PRO1312 nucleic acids

ABSTRACT

The present invention is directed to novel polypeptides and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention.

RELATED APPLICATIONS

This application is a continuation of, and claims priority under 35 USC§120 to, U.S. application Ser. No. 09/941,992 filed Aug. 28, 2001, whichis a continuation of, and claims priority under 35 USC §120 to, PCTApplication PCT/US00/08439 filed Mar. 30, 2000, which is acontinuation-in-part of, and claims priority under 35 USC §120 to, PCTApplication PCT/US00/05841 filed Mar. 2, 2000, which is acontinuation-in-part of, and claims priority under 35 USC §120 to, PCTApplication PCT/US99/28313 filed Nov. 30, 1999, which is acontinuation-in-part of, and claims priority under 35 USC §120 to, U.S.application Ser. No. 09/380,137 filed Aug. 25, 1999 now abandoned, whichis the National Stage filed under 35 USC §371 of PCT ApplicationPCT/US99/12252 filed Jun. 2, 1999, which claims priority under 35 USC§119 to U.S. Provisional Application Ser. No. 60/096,960 filed Aug. 18,1998.

FIELD OF THE INVENTION

The present invention relates generally to the identification andisolation of novel DNA and to the recombinant production of novelpolypeptides.

BACKGROUND OF THE INVENTION

Extracellular proteins play important roles in, among other things, theformation, differentiation and maintenance of multicellular organisms.The fate of many individual cells, e.g., proliferation, migration,differentiation, or interaction with other cells, is typically governedby information received from other cells and/or the immediateenvironment. This information is often transmitted by secretedpolypeptides (for instance, mitogenic factors, survival factors,cytotoxic factors, differentiation factors, neuropeptides, and hormones)which are, in turn, received and interpreted by diverse cell receptorsor membrane-bound proteins. These secreted polypeptides or signalingmolecules normally pass through the cellular secretory pathway to reachtheir site of action in the extracellular environment.

Secreted proteins have various industrial applications, including aspharmaceuticals, diagnostics, biosensors and bioreactors. Most proteindrugs available at present, such as thrombolytic agents, interferons,interleukins, erythropoietins, colony stimulating factors, and variousother cytokines, are secretory proteins. Their receptors, which aremembrane proteins, also have potential as therapeutic or diagnosticagents. Efforts are being undertaken by both industry and academia toidentify new, native secreted proteins. Many efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel secreted proteins. Examples of screening methods andtechniques are described in the literature [see, for example, Klein etal., Proc. Natl. Acad. Sci. 93:7108–7113 (1996); U.S. Pat. No.5,536,637)].

Membrane-bound proteins and receptors can play important roles in, amongother things, the formation, differentiation and maintenance ofmulticellular organisms. The fate of many individual cells, e.g.,proliferation, migration, differentiation, or interaction with othercells, is typically governed by information received from other cellsand/or the immediate environment. This information is often transmittedby secreted polypeptides (for instance, mitogenic factors, survivalfactors, cytotoxic factors, differentiation factors, neuropeptides, andhormones) which are, in turn, received and interpreted by diverse cellreceptors or membrane-bound proteins. Such membrane-bound proteins andcell receptors include, but are not limited to, cytokine receptors,receptor kinases, receptor phosphatases, receptors involved in cell-cellinteractions, and cellular adhesin molecules like selectins andintegrins. For instance, transduction of signals that regulate cellgrowth and differentiation is regulated in part by phosphorylation ofvarious cellular proteins. Protein tyrosine kinases, enzymes thatcatalyze that process, can also act as growth factor receptors. Examplesinclude fibroblast growth factor receptor and nerve growth factorreceptor.

Membrane-bound proteins and receptor molecules have various industrialapplications, including as pharmaceutical and diagnostic agents.Receptor immunoadhesins, for instance, can be employed as therapeuticagents to block receptor-ligand interactions. The membrane-boundproteins can also be employed for screening of potential peptide orsmall molecule inhibitors of the relevant receptor/ligand interaction.

Efforts are being undertaken by both industry and academia to identifynew, native receptor or membrane-bound proteins. Many efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel receptor or membrane-boundproteins.

1. PRO281

A novel gene designated testis enhanced gene transcript (TEGT) hasrecently been identified in humans (Walter et al., Genomics 20:301–304(1995)). Recent results have shown that TEGT protein is developmentallyregulated in the mammalian testis and possesses a nuclear targetingmotif that allows the protein to localize to the nucleus (Walter et al.,Mamm. Genome 5:216–221 (1994)). As such, it is believed that the TEGTprotein plays an important role in testis development. There is,therefore, substantial interest in identifying and characterizing novelpolypeptides having homology to the TEGT protein. We herein describe theidentification and characterization of novel polypeptides havinghomology to TEGT protein, designated herein as PRO281 polypeptides.

2. PRO276

Efforts are being undertaken by both industry and academia to identifynew, native membrane-bound proteins. Many of these efforts are focusedon the screening of mammalian recombinant DNA libraries to identify thecoding sequences for novel membrane-bound proteins. We herein describethe identification and characterization of novel transmembranepolypeptides, designated herein as PRO276 polypeptides.

3. PRO189

Efforts are being undertaken by both industry and academia to identifynew, native secreted proteins. Many of these efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel secreted proteins. We herein describe theidentification and characterization of novel secreted polypeptides,designated herein as PRO189 polypeptides.

4. PRO190

Of particular interest are proteins having seven transmembrane domains(7TM), or more generally, all multiple transmembrane spanning proteins.Among multiple transmembrane spanning proteins are ion channels andtransporters. Examples of transporters are the UDP-galactose transporterdescribed in Ishida, et al., J. Biochem., 120(6):1074–1078 (1996), andthe CMP-sialic acid transporter described in Eckhardt, et al., PNAS,93(15):7572–7576 (1996). We herein describe the identification andcharacterization of novel transmembrane polypeptides, designated hereinas PRO190 polypeptides.

5. PRO341

Efforts are being undertaken by both industry and academia to identifynew, native membrane-bound proteins. Many of these efforts are focusedon the screening of mammalian recombinant DNA libraries to identify thecoding sequences for novel membrane-bound proteins. We herein describethe identification and characterization of novel transmembranepolypeptides, designated herein as PRO341 polypeptides.

6. PRO180

Efforts are being undertaken by both industry and academia to identifynew, native membrane-bound proteins. Many of these efforts are focusedon the screening of mammalian recombinant DNA libraries to identify thecoding sequences for novel membrane-bound proteins. We herein describethe identification and characterization of novel transmembranepolypeptides, designated herein as PRO180 polypeptides.

7. PRO194

Efforts are being undertaken by both industry and academia to identifynew, native membrane-bound proteins. Many of these efforts are focusedon the screening of mammalian recombinant DNA libraries to identify thecoding sequences for novel membrane-bound proteins. We herein describethe identification and characterization of novel transmembranepolypeptides, designated herein as PRO194 polypeptides.

8. PRO203

Enzymatic proteins play important roles in the chemical reactionsinvolved in the digestion of foods, the biosynthesis of macromolecules,the controlled release and utilization of chemical energy, and otherprocesses necessary to sustain life. ATPases are a family of enzymesthat play a variety of important roles, including energizing transportof ions and molecules, across cellular membranes. Transport mechanismsthat employ ATPases often involve excluding xeno- and endobiotic toxinsfrom the cellular environment, thereby protecting cells from toxicity ofthese compounds. Lu et al. report a detoxification mechanism whereglutathione S-transferase (GST) catalyzes glutathionation of planttoxins, and a specific Mg²⁺-ATPase is involved in the transport of theglutathione S-conjugates from the cytosol. Proc. Natl. Acad. Sci. USA94(15):8243–8248 (1997). This study and others indicate the importanceof the identification of ATPases, such as GST ATPases, and of novelproteins having sequence identity with ATPases.

More generally, and also of interest are novel membrane-bound proteins,including those which may be involved in the transport of ions andmolecules across membranes. Membrane-bound proteins and receptors canplay an important role in the formation, differentiation and maintenanceof multicellular organisms. The fate of many individual cells, e.g.,proliferation, migration, differentiation, or interaction with othercells, is typically governed by information received from other cellsand/or the immediate environment. This information is often transmittedby secreted polypeptides (for instance, mitogenic factors, survivalfactors, cytotoxic factors, differentiation factors, neuropeptides, andhormones) which are, in turn, received and interpreted by diverse cellreceptors or membrane-bound proteins. Such membrane-bound proteins andcell receptors include, but are not limited to, cytokine receptors,receptor kinases, receptor phosphatases, receptors involved in cell-cellinteractions, and cellular adhesin molecules like selectins andintegrins. For instance, transduction of signals that regulate cellgrowth and differentiation is regulated in part by phosphorylation ofvarious cellular proteins. Protein tyrosine kinases, enzymes thatcatalyze that process, can also act as growth factor receptors. Examplesinclude fibroblast growth factor receptor and nerve growth factorreceptor.

In light of the important physiological roles played by ATPases andmembrane-bound proteins efforts are being undertaken by both industryand academia to identify new, native membrane-bound proteins, andproteins having sequence identity to ATPases. We herein describe theidentification and characterization of novel polypeptides havingsequence identity to GST ATPase, designated herein as PRO203polypeptides.

9. PRO290

Of particular interest are novel proteins and nucleic acids which havesequence identity with known proteins and nucleic acids. Proteins ofinterest which are well known in the art include NTII-1, a nerve proteinwhich facilitates regeneration, FAN, and beige. Beige, or bg, is amurine analog related to Chediak-Higashi Syndrome (CHS), a rareautosomal recessive disease in which neutrophils, monocytes andlymphocytes contain giant cytoplasmic granules. See Perou et al., J.Biol. Chem. 272(47):29790 (1997) and Barbosa et al., Nature 382:262(1996).

We herein describe the identification and characterization of novelpolypeptides having sequence identity to NTII-1, FAN and beige,designated herein as PRO290 polypeptides.

10. PRO874

Efforts are being undertaken by both industry and academia to identifynew, native membrane-bound proteins. Many of these efforts are focusedon the screening of mammalian recombinant DNA libraries to identify thecoding sequences for novel membrane-bound proteins. We herein describethe identification and characterization of novel transmembranepolypeptides, designated herein as PRO194 polypeptides.

11. PRO710

In Saccharomyces cerevisiae, the chromatin structure of DNA replicationorigins changes as cells become competent for DNA replication,suggesting that G1 phase-specific association of replication factorswith origin DNA regulates entry into S phase (Aparicio et al., Cell91:59–69 (1997)). In fact, it has been shown that the initiation of DNAreplication in Saccharomyces cerevisiae requires the protein product ofthe CDC45 gene which encodes a protein that stays at relatively constantlevels throughout the cell cycle (Owens et al., Proc. Natl. Acad. SciUSA 94:12521–12526 (1997)). The CDC45 protein is part of aprereplication complex that may move with DNA replication forks inyeast. Given the obvious importance of the CDC45 protein in DNAreplication, there is significant interest in identifying andcharacterizing novel polypeptides having homology to CDC45. We hereindescribe the identification and characterization of novel polypeptideshaving homology to the CDC45 protein, designated herein as PRO710polypeptides.

12. PRO1151

The complement proteins comprise a large group of serum proteins some ofwhich act in an enzymatic cascade, producing effector molecules involvedin inflammation. The complement proteins are of particular importance inregulating movement and function of cells involved in inflammation. Oneof the complement proteins, C1q, has been shown to be involved in therecognition of microbial surfaces and antibody-antigen complexes in theclassical pathway of complement (Shapiro et al., Curr. Biol.8(6):335–338 (1998)).

Given the physiological importance of inflammation and relatedmechanisms in vivo and in the specific physiological activities ofcomplement C1q protein, efforts are currently being undertaken toidentify new, native proteins which share sequence similarity to thecomplement proteins. We herein describe the identification andcharacterization of novel polypeptides having homology to complement C1qprotein, designated herein as PRO1151 polypeptides.

13. PRO1282

All proteins containing leucine-rich repeats are thought to be involvedin protein-protein interactions. Leucine-rich repeats are short sequencemotifs present in a number of proteins with diverse functions andcellular locations. The crystal structure of ribonuclease inhibitorprotein has revealed that leucine-rich repeats correspond to beta-alphastructural units. These units are arranged so that they form a parallelbeta-sheet with one surface exposed to solvent, so that the proteinacquires an unusual, nonglubular shape. These two features have beenindicated as responsible for the protein-binding functions of proteinscontaining leucine-rich repeats. See, Kobe and Deisenhofer, TrendsBiochem. Sci., 19(10):415–421 (October 1994); Kobe and Deisenhofer,Curr. Opin. Struct. Biol., 5(3):409–416 (1995).

A study has been reported on leucine-rich proteoglycans which serve astissue organizers, orienting and ordering collagen fibrils duringontogeny and are involved in pathological processes such as woundhealing, tissue repair, and tumor stroma formation. Iozzo, R. V., Crit.Rev. Biochem. Mol. Biol., 32(2):141–174 (1997). Others studiesimplicating leucine rich proteins in wound healing and tissue repair areDe La Salle, C., et al., Vouv. Rev. Fr. Hematol. (Germany),37(4):215–222 (1995), reporting mutations in the leucine rich motif in acomplex associated with the bleeding disorder Bernard-Soulier syndrome,Chlemetson, K. J., Thromb. Haemost. (Germany), 74(1):111–116 (July1995), reporting that platelets have leucine rich repeats and Ruoslahti,E. I., et al., WO9110727-A by La Jolla Cancer Research Foundationreporting that decorin binding to transforming growth factory hasinvolvement in a treatment for cancer, wound healing and scarring.Related by function to this group of proteins is the insulin like growthfactor (IGF), in that it is useful in wound-healing and associatedtherapies concerned with re-growth of tissue, such as connective tissue,skin and bone; in promoting body growth in humans and animals; and instimulating other growth-related processes. The acid labile subunit ofIGF (ALS) is also of interest in that it increases the half-life of IGFand is part of the IGF complex in vivo.

Another protein which has been reported to have leucine-rich repeats isthe SLIT protein which has been reported to be useful in treatingneuro-degenerative diseases such as Alzheimer's disease, nerve damagesuch as in Parkinson's disease, and for diagnosis of cancer, see,Artavanistsakonas, S. and Rothberg, J. M., WO9210518-A1 by YaleUniversity. Of particular interest is LIG-1, a membrane glycoproteinthat is expressed specifically in glial cells in the mouse brain, andhas leucine rich repeats and immunoglobulin-like domains. Suzuki, etal., J. Biol. Chem. (U.S.), 271(37):22522 (1996). Other studiesreporting on the biological functions of proteins having leucine richrepeats include: Tayar, N., et al., Moll. Cell Endocrinol., (Ireland),125(1–2):65–70 (December 1996) (gonadotropin receptor involvement);Miura, Y., et al., Nippon Rinsho (Japan), 54(7):1784–1789 (July 1996)(apoptosis involvement); Harris, P. C., et al., J. Am. Soc. Nophrol.,6(4):1125–1133 (October 1995) (kidney disease involvement).

Leucine rich repeat proteins are further discussed in Kajava, J. Mol.Biol., 277(3):519–527 (1998), Nagasawa, et al., Genomics, 44(3):273–279(1997), Bengtsson, J. Biol. Chem., 270(43):25639–25644(1995), Gaillard,et al., Cell, 65(7):1127–1141 (1991) and Ohkura and Yanagida, Cell,64(1):149–157 (1991), all incorporated herein by reference.

Thus, due to all the reasons listed above, new members of the leucinerich repeat superfamily are of interest. On a more general level, allnovel proteins are of interest. We herein describe the identificationand characterization of novel leucine-rich repeat-containingpolypeptides, designated herein as PRO1282 polypeptides.

14. PRO358

The cloning of the Toll gene of Drosophila, a maternal effect gene thatplays a central role in the establishment of the embryonicdorsal-ventral pattern, has been reported by Hashimoto et al., Cell52:269–279 (1988). The Drosophila Toll gene encodes an integral membraneprotein with an extracytoplasmic domain of 803 amino acids and acytoplasmic domain of 269 amino acids. The extracytoplasmic domain has apotential membrane-spanning segment, and contains multiple copies of aleucine-rich segment, a structural motif found in many transmembraneproteins. The Toll protein controls dorsal-ventral patterning inDrosophila embryos and activates the transcription factor Dorsal uponbinding to its ligand Spätzle. (Morisato and Anderson, Cell 76:677–688(1994)). In adult Drosophila, the Toll/Dorsal signaling pathwayparticipates in the anti-fungal immune response. (Lenaitre et al., Cell86:973–983 (1996)).

A human homologue of the Drosophila Toll protein has been described byMedzhitov et al., Nature 388:394–397 (1997). This human Toll, just asDrosophila Toll, is a type I transmembrane protein, with anextracellular domain consisting of 21 tandemly repeated leucine-richmotifs (leucine-rich region—LRR), separated by a non-LRR region, and acytoplasmic domain homologous to the cytoplasmic domain of the humaninterleukin-1 (IL-1) receptor. A constitutively active mutant of thehuman Toll transfected into human cell lines was shown to be able toinduce the activation of NF-κB and the expression of NF-κB-controlledgenes for the inflammatory cytolines IL-1, IL-6 and IL-8, as well as theexpression of the constimulatory molecule B7.1, which is required forthe activation of native T cells. It has been suggested that Tollfunctions in vertebrates as a non-clonal receptor of the immune system,which can induce signals for activating both an innate and an adaptiveimmune response in vertebrates. The human Toll gene reported byMedzhitov et al., supra was most strongly expressed in spleen andperipheral blood leukocytes (PBL), and the authors suggested that itsexpression in other tissues may be due to the presence of macrophagesand dendritic cells, in which it could act as an early-warning systemfor infection. The public GenBank database contains the following Tollsequences: Toll1 (DNAX# HSU88540-1, which is identical with the randomsequenced full-length cDNA #HUMRSC786-1); Toll2 (DNAX# HSU88878-1);Toll3 (DNAX# HSU88879-1); and Toll4 (DNAX# HSU88880-1, which isidentical with the DNA sequence reported by Medzhitov et al., supra). Apartial Toll sequence (Toll5) is available from GenBank under DNAX#HSU88881-1.

Further human homologues of the Drosophila Toll protein, designated asToll-like receptors (huTLRs1–5) were recently cloned and shown to mirrorthe topographic structure of the Drosophila counterpart (Rocket al.,Proc. Natl. Acad. Sci. USA 95:588–593 [1998]). Over expression of aconstitutively active mutant of one human TLR (Toll-proteinhomologue—Medzhitov et al., supra; TLR4—Rock et al., supra) leads to theactivation of NF-κB and induction of the inflammatory cytokines andconstimulatory molecules. Medzhitov et al., supra.

We herein describe the identification and characterization of novelpolypeptides having homology to Toll, designated herein as PRO358polypeptides.

15. PRO1310

Of interest are proteins related to carboxypeptidases. Variouscarboxypeptidases are described in the literature, i.e., Krause et al.,Immunol. Rev. 161:119–127 (1998) and Leiter, J. Endocrinol.155(2):211–214 (1997). We herein describe the identification andcharacterization of novel polypeptides having homology to acarboxypeptidase, designated herein as PRO1310 polypeptides.

16. PRO698

The extracellular mucous matrix of olfactory neuroepithelium is a highlyorganized structure in intimate contact with chemosensory cilia thathouse the olfactory transduction machinery. The major protein componentof this extracellular matrix is olfactomedin, a glycoprotein that isexpressed in olfactory neuroepithelium and which form intermoleculardisulfide bonds so as to produce a polymer (Yokoe et al., Proc. Natl.Acad. Sci. USA 90:4655–4659 (1993), Bal et al., Biochemistry32:1047–1053 (1993) and Snyder et al., Biochemistry 30:9143–9153(1991)). It has been suggested that olfactomedin may influence themaintenance, growth or differentiation of chemosensory cilia on theapical dendrites of olfactory neurons. Given this important role, thereis significant interest in identifying and characterizing novelpolypeptides having homology to olfactomedin. We herein describe theidentification and characterization of novel polypeptides havinghomology to olfactomedin protein, designated herein as PRO698polypeptides.

17. PRO732

Efforts are being undertaken by both industry and academia to identifynew, native membrane-bound proteins. Many of these efforts are focusedon the screening of mammalian recombinant DNA libraries to identify thecoding sequences for novel membrane-bound proteins. We herein describethe identification and characterization of novel transmembranepolypeptides having sequence identity to the Diff33 protein, designatedherein as PRO732 polypeptides.

18. PRO1120

Enzymatic proteins play important roles in the chemical reactionsinvolved in the digestion of foods, the biosynthesis of macromolecules,the controlled release and utilization of chemical energy, and otherprocesses necessary to sustain life. Sulfatases are a family of secretedenzymatic proteins that play a variety of important metabolic roles andthus are the subject of interest in research and industry (see, e.g.,Sleat et al., Biochem J., 324(Pt. 1):33–39 (1997)). Deficiencies ofcertain sulfatases have been implicated in various human disordersincluding Sanfilippo D syndrome (see, Litjens et al., Biochem J. 327(Pt1):899–94 (1997); Leipprandt et al. J. Inherit Metab. Dis. 18(5):647–648(1995); and Freeman et al. Biochem J. 282(pt2):605–614 (1992)). Weherein describe the identification and characterization of novelpolypeptides having sequence identity to sulfatase protein, designatedherein as PRO1120 polypeptides.

19. PRO537

Efforts are being undertaken by both industry and academia to identifynew, native secreted proteins. Many of these efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel secreted proteins. We herein describe theidentification and characterization of novel secreted polypeptides,designated herein as PRO537 polypeptides.

20. PRO536

Efforts are being undertaken by both industry and academia to identifynew, native secreted proteins. Many of these efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel secreted proteins. We herein describe theidentification and characterization of novel secreted polypeptides,designated herein as PRO536 polypeptides.

21. PRO535

Isomerase proteins play many important physiological roles in themammal. Many different types of isomerase proteins have been identifiedand characterized including, for example, protein disulfide isomerasesand peptidyl-prolyl isomerases. It has been reported that manyimmunophilin proteins, i.e., proteins that serves as receptors forimmunosuppressant drugs, exhibit peptidyl-prolyl isomerase activity inthat they function to catalyze the interconversion of the cis and transisomerase of peptide and protein substrates for immunophilin proteins.As such, there is significant interest in identifying and characterizingnovel polypeptides having sequence similarity to peptidyl-prolylisomerase proteins. We herein describe the identification andcharacterization of novel polypeptides having homology to a putativepeptidyl-prolyl isomerase protein, designated herein as PRO535polypeptides.

22. PRO718

Efforts are being undertaken by both industry and academia to identifynew, native transmembrane proteins. Many of these efforts are focused onthe screening of mammalian recombinant DNA libraries to identify thecoding sequences for novel transmembrane proteins. We herein describethe identification and characterization of novel transmembranepolypeptides, designated herein as PRO718 polypeptides.

23. PRO872

Enzymatic proteins play important roles in the chemical reactionsinvolved in the digestion of foods, the biosynthesis of macromolecules,the controlled release and utilization of chemical energy, and otherprocesses necessary to sustain life. Dehydrogenases and desaturases area family of enzymes that play a variety of important metabolic roles andthus are the subject of interest in research and industry (see Hable etal., Mol. Gen. Genet. 257(2):167–176 (1998); Schneider, C. et al., Prot.Expr. Purif. 10(2):175–179 (1997)). We herein describe theidentification and characterization of novel polypeptides havingsequence identity to dehydrogenase proteins, designated herein as PRO872polypeptides.

24. PRO1063

Collagens constitute the most abundant proteins of the extracellularmatrix (ECM) in mammalian organisms. Collagen and other macromoleculesof the ECM are deposited by resident cells and organized into athree-dimensional meshwork. This ECM environment plays an essential rolein guiding cell migration and in cell-to-cell communication duringmorphogenic processes. The restructuring of the ECM during remodelingoccurs as a cooperative multistep process involving a localizeddegradation of existing macromolecules, rearrangement of thecytoskeleton, cell translocation, and deposition of new ECM components.Involved in this restructuring are enzymes such as collagenases andgelatinases which play important roles in the degradation of the ECM. Inlight of the obviously important roles played by the collagenaseenzymes, there is substantial interest in identifying and characterizingnovel polypeptides having homology to these proteins. We herein describethe identification and characterization of novel polypeptides havinghomology to human type IV collagenase protein, designated herein asPRO1063 polypeptides.

25. PRO619

Immunoglobulins are antibody molecules, the proteins that function bothas receptors for antigen on the B-cell membrane and as the secretedproducts of the plasma cell. Like all antibody molecules,immunoglobulins perform two major functions: they bind specifically toan antigen and they participate in a limited number of biologicaleffector functions. Therefore, new members of the Ig superfamily arealways of interest.

Of particular interest are novel gene products associated with mu chainsin immature B cells. Shirasawa, et al., EMBO J., 12(5):1827–1834 (1993);Dul, et al., Eur. J. Immunol., 26(4):906–913 (1996). Moreover, themolecular components and assembly of mu surrogate light chain complexesin pre-B cell lines are of interest. Ohnishi and Takemori, J. Biol.Chem., 269(45):28347–28353 (1994); Bauer, et al., Curr. Top. Microbiol.,137:130–135 (1988). Novel nucleic acids and peptides related to VpreB1,VpreB2 and VpreB3 by sequence identity are of particular interest. Theassembly and manipulation of immunoglobulins can effect the entireindustry related to antibodies and vaccines.

We herein describe the identification and characterization of novelpolypeptides having homology to VpreB proteins, designated herein asPRO619 polypeptides.

26. PRO943

Fibroblast growth factor (FGF) proteins exhibit a variety of activitiesand act by binding to cell surface fibroblast growth factor receptors.Many different fibroblast growth factor receptors have been identifiedand characterized, including the fibroblast growth factor receptor-4,which has been shown to be a high affinity receptor for both acidic andbasic FGF (Ron et al., J. Biol. Chem. 268:5388–5394 (1993) and Stark etal., Development 113:641–651 (1991)). Given the obvious importance ofthe FGF family of proteins and the cell surface receptors to which theybind, there is significant interest in identifying novel polypeptideshaving homology to the FGF receptor family. We herein describe theidentification and characterization of novel polypeptides havinghomology to the fibroblast growth factor receptor-4 protein, designatedherein as PRO943 polypeptides.

27. PRO1188

The identification of nucleotide pyrophosphohydrolases has been ofinterest because of the potential roles these secreted molecules play incalcium pyrophosphate dihydrate (CPPD) deposition disease, arthritis,and other joint diseases (see Masuda et al. J. Rheumatol. (997)24(8):1588–1594; and Terkeltaub et al., Arthritis Rheum (1998)37(6):934–941). We herein describe the identification andcharacterization of novel polypeptides having homology to nucleotidepyrophosphohydrolases, designated herein as PRO1188 polypeptides.

28. PRO1133

Netrins are molecules that guide growing axons and that are strikinglysimilar in sequence and in function in flies, nematodes and vertebrates.Additionally, netrin receptors have been identified in all three animalgroups and shown to have crucial, conserved roles in axon navigation.Netrins and their receptors are further described in the literature,i.e., Varela-Echavarria and Guthrie, Genes Dev., 11(5):545–557 (1997);Guthrie, Curr. Biol., 7(1):R6–R9 (1997); and Keynes and Cook, Neuron,17(6):1031–1034 (1996). Due to their relation to neurons, netrins andtheir related proteins are of interest. Of particular interest aremolecules having sequence identity or similarity with netrin. We hereindescribe the identification and characterization of novel polypeptideshaving homology to netrins, designated herein as PRO1133 polypeptides.

29. PRO784

Of interest are membrane-bound and receptor proteins involved inintracellular signaling, metabolism, transport, and other pathways. Forexample, membrane-bound proteins of the endoplasmic reticulum and golgiapparatus play important roles in the transport of proteins. The sec22protein is an endoplasmic reticulum membrane-bound protein involved infundamental membrane trafficking reactions where secretory products arerouted from their site of synthesis to their final destination. Theroles of sec22 in transport pathways have been reported by numerousinvestigators (see Tang et al., Biochem Biophys Res Commun243(3):885–891 (1998); Hay et al., J. Biol. Chem. 271(10):5671–5679(1996); and Newman et al., Moll. Cell. Biol. 10(7):3405–3414 (1990)). Weherein describe the identification and characterization of novelpolypeptides having homology to sec22, designated herein as PRO784polypeptides.

30. PRO783

Efforts are being undertaken by both industry and academia to identifynew, native membrane-bound proteins. Many of these efforts are focusedon the screening of mammalian recombinant DNA libraries to identify thecoding sequences for novel membrane-bound proteins. We herein describethe identification and characterization of novel transmembranepolypeptides, designated herein as PRO783 polypeptides.

31. PRO820

Immunoglobulin molecules play roles in many important mammalianphysiological processes. The structure of immunoglobulin molecules hasbeen extensively studied and it has been well documented that intactimmunoglobulins possess distinct domains, one of which is the constantdomain or F_(c) region of the immunoglobulin molecule. The F_(c) domainof an immunoglobulin, while not being directly involved in antigenrecognition and binding, does mediate the ability of the immunoglobulinmolecule, either uncomplexed or complexed with its respective antigen,to bind to F_(c) receptors either circulating in the serum or on thesurface of cells. The ability of an F_(c) domain of an immunoglobulin tobind to an F_(c) receptor molecule results in a variety of importantactivities, including for example, in mounting an immune responseagainst unwanted foreign particles. Thus, molecules related to F_(c)receptors are of interest. F_(c) receptors are further described inTominaga et al., Biochem. Biophys. Res. Commun., 168(2):683–689 (1990);Zhang et al., Immuno., 39(6):423–427 (1994). We herein describe theidentification and characterization of novel polypeptides havinghomology to F_(c) receptor, designated herein as PRO820 polypeptides.

32. PRO1080

The folding of proteins and the assembly of protein complexes withinsubcompartments of the eukaryotic cell is catalysed by different membersof the Hsp70 protein family. The chaperone function of Hsp70 proteins inthese events is regulated by members of the DnaJ-like protein family,which occurs through direct interaction of different Hsp70 and DnaJ-likeprotein pairs that appear to be specifically adapted to each other. Thediversity of functions of DnaJ-like proteins using specific examples ofDnaJ-Hsp70 interactions with polypeptides in yeast protein-biogenesispathways is further described in Cyr et al., Trends Biochem. Sci.,19(4):176–181 (1994). DnaJ proteins and their involvement in the bindingof secretory precursor polypeptides to a translocon subcomplex andpolypeptide translocation machinery in the yeast endoplasmic reticulumare further described in Lyman and Schekinan, Cell 88(1):85–96 (1997)and Lyman and Schekman, Experientia 52(12):1042–1049 (1996),respectively. Thus, DnaJ proteins are of interest, as are proteinsrelated to DnaJ proteins, particularly those having sequence identitywith DnaJ proteins. We herein describe the identification andcharacterization of novel polypeptides having homology to DnaJ proteins,designated herein as PRO1080 polypeptides.

33. PRO1079

Efforts are being undertaken by both industry and academia to identifynew, native secreted proteins. Many of these efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel secreted proteins. We herein describe theidentification and characterization of novel secreted polypeptides,designated herein as PRO1079 polypeptides.

34. PRO793

Efforts are being undertaken by both industry and academia to identifynew, native membrane-bound proteins. Many of these efforts are focusedon the screening of mammalian recombinant DNA libraries to identify thecoding sequences for novel membrane-bound proteins. We herein describethe identification and characterization of novel transmembranepolypeptides, designated herein as PRO793 polypeptides.

35. PRO1016

Enzymatic proteins play important roles in the chemical reactionsinvolved in the digestion of foods, the biosynthesis of macromolecules,the controlled release and utilization of chemical energy, and otherprocesses necessary to sustain life. Acyltransferases are enzymes whichacylate moieties. Acyl-glycerol-phosphate acyltransferases can act onlysophosphatidic acid as a substrate. The lysophosphatidic acid isconverted to phophatidic acid and thus plays a role in formingphosphatidylethanolamine found in membranes. See, Brown, et al., PlantMol. Biol., 26(1):211–223 (1994). Thus, acyltransferases play animportant role in the biosynthesis of molecules requiring acylation. Weherein describe the identification and characterization of novelpolypeptides having homology to acyltransferase proteins, designatedherein as PRO1016 polypeptides.

36. PRO1013

Efforts are being undertaken by both industry and academia to identifynew, native proteins. Many of these efforts are focused on the screeningof mammalian recombinant DNA libraries to identify the coding sequencesfor novel proteins. We herein describe the identification andcharacterization of novel polypeptides, designated herein as PRO1013polypeptides.

37. PRO937

The glypican family of heparan sulfate proteoglyeans are majorcell-surface proteoglycans of the developing nervous system. It isbelieved that members of the glypican family play a role in regulatingcell cycle progression during the transition of proliferating neuronalprogenitor cells to differentiated neurons. Lander et al. Perspect Dev.Neurobiol 3(4):347–358 (1996). It is likely that proteoglycans of theglypican family play other important roles in neural development (Landeret al., supra), and as well as other tissues, as glypican family membershave also been found in the developing kidney (Watanabe et al. J. CellBiol. 130(5):1207–1218 (1995)). Accordingly, the identification of newmembers of the glypican family of proteins is of interest in researchand in industry.

Described herein is the identification and characterization of novelpolypeptides having sequence identity with glypican family proteins,designated herein as PRO937 polypeptides.

38. PRO842

Efforts are being undertaken by both industry and academia to identifynew, native secreted proteins. Many of these efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel secreted proteins. We herein describe theidentification and characterization of novel secreted polypeptides,designated herein as PRO842 polypeptides.

39. PRO839

Efforts are being undertaken by both industry and academia to identifynew, native secreted proteins. Many of these efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel secreted proteins. We herein describe theidentification and characterization of novel secreted polypeptides,designated herein as PRO839 polypeptides.

40. PRO1180

Methyltransferase enzymes catalyze the transfer of methyl groups from adonor molecule to an acceptor molecule Methyltransferase enzymes playextremely important roles in a number of different biological processesincluding, for example, in the electron transport chain in the plasmamembrane in prokaryotes and in the inner mitochondrial membrane ineukaryotic cells (see, e.g., Barkovich et al., J. Biol. Chem.272:9182–9188 (1997), Dibrov et al., J. Biol. Chem. 272:9175–9181(1997), Lee et al., J. Bacteriol., 179:1748–1754 (1997) and Marbois etal., Arch. Biochem. Biophys. 313:83–88 (1994)). Methyltransferaseenzymes have been shown to be essential for the biosynthesis ofubiquinone (coenzyme Q) and menaquinone at (vitamin K2), both of whichare essential isoprenoid quinone components of the respiratory electrontransport chain. Given the obvious importance of the methyltransferaseenzymes, there is substantial interest in identifying novel polypeptidehomologs of the methyltransferases. We herein describe theidentification and characterization of a novel polypeptide havinghomology to methyltransferase enzymes, designated herein as PRO1180polypeptides.

41. PRO1134

Efforts are being undertaken by both industry and academia to identifynew, native secreted proteins. Many of these efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel secreted proteins. We herein describe theidentification and characterization of novel secreted polypeptides,designated herein as PRO1134 polypeptides.

42. PRO830

Efforts are being undertaken by both industry and academia to identifynew, native secreted proteins. Many of these efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel secreted proteins. We herein describe theidentification and characterization of novel secreted polypeptides,designated herein as PRO830 polypeptides.

43. PRO1115

Efforts are being undertaken by both industry and academia to identifynew, native membrane-bound proteins. Many of these efforts are focusedon the screening of mammalian recombinant DNA libraries to identify thecoding sequences for novel membrane-bound proteins. We herein describethe identification and characterization of novel transmembranepolypeptides, designated herein as PRO1115 polypeptides.

44. PRO1277

Efforts are being undertaken by both industry and academia to identifynew, native proteins. Many efforts are focused on the screening ofmammalian recombinant DNA libraries to identify the coding sequences fornovel receptor and other proteins. Of interest is the identification ofproteins that may play roles in various human disorders and dysfunction.For example, the identification of proteins of the ear and the functionsthey play in hearing may lead to an understanding of the causes ofhearing loss and deafness. Coch-B2 is one such protein that has beenfound to be specifically expressed in the inner ear (cochlea). It hasbeen characterized and studied for its possible role in hearing loss(Robertson et al. Genomics (1994) 23(1):52–50; Robertson et al. Genomics(1997) 46(3):345–354). We herein describe the identification andcharacterization of novel polypeptides having sequence identity toCoch-B2, designated herein as PRO1277 polypeptides.

45. PRO1135

Glycosylation is an important mechanism for modulating thephysiochemical and biological properties of proteins in a stage- andtissue-specific manner. One of the important enzymes involved inglycosylation in Saccharomyces cerevisiae is alpha 1,2-mannosidase, anenzyme that catalyzes the conversion of Man9GlcNAc2 to Man8GlcNAc2during the formation of N-linked oligosaccharides. The Saccharomycescerevisiae alpha 1,2-mannosidase enzyme of is a member of the Class Ialpha 1,2-mannosidases that are conserved from yeast to mammals. Giventhe important roles played by the alpha 1,2-mannosidases inglycosylation and the physiochemical activity regulated byglycosylation, there is significant interest in identifying novelpolypeptides having homology to one or more mannosidases. We hereindescribe the identification and characterization of novel polypeptideshaving homology to alpha 1,2-mannosidase protein, designated herein asPRO1135 polypeptides.

46. PRO1114

Interferons (IFNs) encompass a large family of secreted proteinsoccurring in vertebrates. Although they were originally named for theirantiviral activity, growing evidence supports a critical role for IFNsin cell growth and differentiation (Jaramillo et al., CancerInvestigation 13(3):327–338 (1995)). IFNs belong to a class of negativegrowth factors having the ability to inhibit the growth of a widevariety of cells with both normal and transformed phenotypes. IFNtherapy has been shown to be beneficial in the treatment of humanmalignancies such as Karposi's sarcoma, chronic myelogenous leukemia,non-Hodgkin's lymphoma, and hairy cell leukemia as well as in thetreatment of infectious diseases such as hepatitis B (Gamliel et al.,Scanning Microscopy 2(1):485–492 (1988), Einhorn et al., Med. Oncol. &Tumor Pharmacother. 10:25–29 (1993), Ringenberg et al., MissouriMedicine 85(1):21–26 (1988), Saracco et al., Journal of Gastroenterologyand Hepatology 10:668–673 (1995), Gonzalez-Mateos et al.,Hepato-Gastroenterology 42:893–899 (1995) and Malaguamera et al.,Pharmacotherapy 17(5):998–1005 (1997)).

Interferons can be classified into two major groups based upon theirprimary sequence. Type I interferons, IFN-α and IFN-β, are encoded by asuperfamily of intronless genes consisting of the IFN-α gene family anda single IFN-β gene that are thought to have arisen from a commonancestral gene. Type I interferons may be produced by most cell types.Type II IFN, or IFN-γ, is restricted to lymphocytes (T cells and naturalkiller cells) and is stimulated by nonspecific T cell activators orspecific antigens in vivo.

Although both type I and type II IFNs produce similar antiviral andantiproliferative effects, they act on distinct cell surface receptors,wherein the binding is generally species specific (Langer et al.,Immunol. Today 9:393–400 (1988)). Both IFN-α and IFN-β bindcompetitively to the same high affinity type I receptor, whereas IFN-γbinds to a distinct type II receptor. The presence and number of IFNreceptors on the surface of a cell does not generally reflect thesensitivity of the cell to IFN, although it is clear that the effects ofthe IFN protein is mediated through binding to a cell surface interferonreceptor. As such, the identification and characterization of novelinterferon receptor proteins is of extreme interest.

We herein describe the identification and characterization of novelinterferon receptor polypeptides, designated herein as “PRO1114interferon receptor” polypeptides. Thus, the PRO1114 polypeptides of thepresent invention represents a novel cell surface interferon receptor.

47. PRO828

Glutathione peroxidases are of interest because they play importantroles in protection against risk of coronary disease, atherosclerosis,platelet hyperaggregation and synthesis of proaggregant andproinflammatory compounds. Glutathione peroxidases are involved in thereduction of hydrogen peroxides and lipid peroxides, which in turnregulate the activities of cyclooxygenase and lipooxygenase pathways.This ultimately influences the production of eicosanoids and modulatesthe balance between a proaggregatory and antiaggregatory state ofplatelets. These and other activities and functions of glutathioneperoxidases are discussed in greater detail by Ursini et al., Biomed.Environ. Sci 10(2–3): 327–332 (1997); Vitoux et al., Ann. Biol. Clin(Paris) 54(5): 181–187 (1996); and Mirault et al., Ann N.Y. Acad. Sci738: 104–115 (1994).

We herein describe the identification and characterization of novelpolypeptides having sequence identity with glutathione peroxidases,designated herein as PRO828 polypeptides.

48. PRO1009

Long chain acyl-CoA synthetase converts free fatty acids to acyl-CoAesters. This synthetase has been reported to have interestingcharacteristics. Specifically, it has been reported that two boys havingAlport syndrome, elliptocytosis and mental retardation carried a largedeletion where long chain acyl-CoA synthetase 4 would have been located.Thus, the absence of this enzyme is believed to play a role in thedevelopment of mental retardation or other signs associated with Alportsyndrome in the family. Piccini, et al., Genomics, 47(3):350–358 (1998).Moreover, it has been reported that an inhibitor of acyl coenzyme Asynthetase, triacsin C, inhibits superoxide anion generation anddegranulation by human neutrophils. Thus, it is suggested that there isa role for acyl-CoA esters in regulating activation of O₂ generation anddegranulation at the G protein or subsequent step(s). Korchak, et al.,J. Biol. Chem., 269(48):30281–30287 (1994). Long chain acyl-CoAsynthetase is also briefly discussed in a report which describes verylong chain acyl-CoA synthetase. Uchiyama, et al., J. Biol. Chem.,271(48):30360 (1994). Thus, long chain acyl-CoA synthetase andparticular novel polypeptides having sequence identity therewith are ofinterest.

We herein describe the identification and characterization of novelpolypeptides having sequence identity with long chain acyl-CoAsynthetase, designated herein as PRO1009 polypeptides.

49. PRO1007

Glycosylphosphatidylinositol (GPI) anchored proteoglycans are generallylocalized to the cell surface and are thus known to be involved in theregulation of responses of cells to numerous growth factors, celladhesion molecules and extracellular matrix components. Themetastasis-associated GPI-anchored protein (MAGPIAP) is one of thesecell surface proteins which appears to be involved in metastasis.Metastasis is the form of cancer wherein the transformed or malignantcells are traveling and spreading the cancer from one site to another.Therefore, identifying the polypeptides related to metastasis andMAGPIAP is of interest.

We herein describe the identification and characterization of novelpolypeptides having sequence identity with MAGPIAP, designated herein asPRO1007 polypeptides.

50. PRO1056

Mammalian cell membranes perform very important functions relating tothe structural integrity and activity of various cells and tissues. Ofparticular interest in membrane physiology is the study oftrans-membrane ion channels which act to directly control a variety ofphysiological, pharmacological and cellular processes. Numerous ionchannels have been identified including calcium (Ca), sodium (Na),chloride (Cl) and potassium (K) channels, each of which have beenanalyzed in detail to determine their roles in physiological processesin vertebrate and insect cells. These roles include such things asmaintaining cellular homeostasis, intracellular signaling, and the like.Given the obvious importance of the ion channels, there is significantinterest in identifying and characterizing novel polypeptides havinghomology to one or more ion channels. We herein describe theidentification and characterization of novel polypeptides havinghomology to a chloride channel protein, designated herein as PRO1056polypeptides.

51. PRO826

Efforts are being undertaken by both industry and academia to identifynew, native secreted proteins. Many of these efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel secreted proteins. We herein describe theidentification and characterization of novel secreted polypeptides,designated herein as PRO826 polypeptides.

52. PRO819

Efforts are being undertaken by both industry and academia to identifynew, native secreted proteins. Many of these efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel secreted proteins. We herein describe theidentification and characterization of novel secreted polypeptides,designated herein as PRO819 polypeptides.

53. PRO1006

Efforts are being undertaken by both industry and academia to identifynew, native secreted proteins. Many of these efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel secreted proteins. We herein describe theidentification and characterization of novel secreted polypeptides,designated herein as PRO1006 polypeptides.

54. PRO1112

Efforts are being undertaken by both industry and academia to identifynew, native membrane-bound proteins. Many of these efforts are focusedon the screening of mammalian recombinant DNA libraries to identify thecoding sequences for novel membrane-bound proteins. We herein describethe identification and characterization of novel transmembranepolypeptides, designated herein as PRO1112 polypeptides.

55. PRO1074

Many membrane-bound enzymatic proteins play important roles in thechemical reactions involved in metabolism, including the biosynthesis ofmacromolecules, the controlled release and utilization of chemicalenergy, development of tissues, and other processes necessary to sustainlife. Galactosyltransferases are a family of enzymes that play a varietyof important metabolic roles and thus are the subject of interest inresearch and industry. Numerous references have been published on theidentification of galactosyltransferases and the roles they play incellular development, maintenance, and dysfunction.

We herein describe the identification and characterization of novelpolypeptides having homology to galactosyltransferases, designatedherein as PRO1074 polypeptides.

56. PRO1005

Efforts are being undertaken by both industry and academia to identifynew, native secreted proteins. Many of these efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel secreted proteins. We herein describe theidentification and characterization of novel secreted polypeptides,designated herein as PRO1005 polypeptides.

57. PRO1073

Efforts are being undertaken by both industry and academia to identifynew, native secreted proteins. Many of these efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel secreted proteins. We herein describe theidentification and characterization of novel secreted polypeptides,designated herein as PRO1073 polypeptides.

58. PRO1152

Efforts are being undertaken by both industry and academia to identifynew, native membrane-bound proteins. Many of these efforts are focusedon the screening of mammalian recombinant DNA libraries to identify thecoding sequences for novel membrane-bound proteins. We herein describethe identification and characterization of novel transmembranepolypeptides, designated herein as PRO1152 polypeptides.

59. PRO1136

PDZ domain-containing proteins assist formation of cell-cell junctionsand localization of membrane protein receptors and ion channels (Danielset al., Nat. Struct. Biol. 5:317–325 (1998) and Ullmer et al., FEBSLett. 424:63–68 (1998)). PDZ domains interact with the C-terminalresidues of a particular target membrane protein. Based on their bindingspecificities and sequence homologies, PDZ domains fall into twoclasses, class I and class II. In light of the obvious importance of thePDZ domain-containing proteins, there is significant interest inidentifying novel polypeptides that have homology to those proteins. Weherein describe the identification and characterization of novelpolypeptides having homology to PDZ domain-containing proteins,designated herein as PRO1136 polypeptides.

60. PRO813

Surfactant proteins play extremely important biological roles in themammalian pulmonary system. One mammalian protein that has been studiedand well characterized is pulmonary surfactant-associated protein C. Forexample, Qanbar et al., Am. J. Physiol. 271:L572–L580 (1996) studied theeffect of palmitoylation of pulmonary surfactant-associated protein C onthe surface activity of phospholipid mixtures. Specifically, the authorsdemonstrated that palmitoylation of pulmonary surfactant-associatedprotein C greatly enhanced lipid respreading and film stability and,therefore, was extremely important for surfactant function. Given theobvious important roles played by surfactant protein in the mammalianorganism, there is significant interest in identifying novelpolypeptides having homology to one or more surfactant enzymes. Weherein describe the identification and characterization of novelpolypeptides having homology to pulmonary surfactant-associated protein,designated herein as PRO813 polypeptides.

61. PRO809

Efforts are being undertaken by both industry and academia to identifynew, native secreted proteins. Many of these efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel secreted proteins. We herein describe theidentification and characterization of novel secreted polypeptides,designated herein as PRO809 polypeptides.

62. PRO791

Of particular interest are novel proteins which have sequence identitywith known proteins. For example, novel proteins having some sequenceidentity with the major histocompatibility complex (MHC) are ofinterest. The MHC complex is a region of multiple loci that play majorroles in determining whether transplanted tissue will be accepted asself (histocompatible) or rejected as foreign (histoincompatible).Moreover, the MHC plays a central role in the development of bothhumoral and cell-mediated immune responses. There are class I, II andIII MHC antigens, all known in the art. Class I antigens areglycoproteins expressed on the surface of nearly all nucleated cells,where they present peptide antigens of altered self-cells necessary forthe activation of Tc cells. The assembly of MHC class I antigens isfurther described in Kvist and Levy, Semin. Immunol., 5(2):105–116(1993) and Maffei, et al., Hum. Immunol., 54(2):91–103 (1997).

We herein describe the identification and characterization of novelpolypeptides having sequence identity to various MHC-I antigens,designated herein as PRO791 polypeptides.

63. PRO1004

Efforts are being undertaken by both industry and academia to identifynew, native secreted proteins. Many of these efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel secreted proteins. We herein describe theidentification and characterization of novel secreted polypeptides,designated herein as PRO1004 polypeptides.

64. PRO1111

Protein-protein interactions include receptor and antigen complexes andsignaling mechanisms. As more is known about the structural andfunctional mechanisms underlying protein-protein interactions,protein-protein interactions can be more easily manipulated to regulatethe particular result of the protein-protein interaction. Thus, theunderlying mechanisms of protein-protein interactions are of interest tothe scientific and medical community.

All proteins containing leucine-rich repeats are thought to be involvedin protein-protein interactions. Leucine-rich repeats are short sequencemotifs present in a number of proteins with diverse functions andcellular locations. The crystal structure of ribonuclease inhibitorprotein has revealed that leucine-rich repeats correspond to beta-alphastructural units. These units are arranged so that they form a parallelbeta-sheet with one surface exposed to solvent, so that the proteinacquires an unusual, nonglubular shape. These two features have beenindicated as responsible for the protein-binding functions of proteinscontaining leucine-rich repeats. See, Kobe and Deisenhofer, TrendsBiochem. Sci., 19(10):415–421 (October 1994).

A study has been reported on leucine-rich proteoglycans which serve astissue organizers, orienting and ordering collagen fibrils duringontogeny and are involved in pathological processes such as woundhealing, tissue repair, and tumor stroma formation. Iozzo, R. V., Crit.Rev. Biochem. Mol. Biol., 32(2):141–174 (1997). Others studiesimplicating leucine rich proteins in wound healing and tissue repair areDe La Salle, C., et al., Vouv. Rev. Fr. Hematol. (Germany),37(4):215–222 (1995), reporting mutations in the leucine rich motif in acomplex associated with the bleeding disorder Bemard-Soulier syndrome,Chlemetson, K. J., Thromb. Haemost. (Germany), 74(1):111–116 (July1995), reporting that platelets have leucine rich repeats and Ruoslahti,E. I., et al., WO9110727-A by La Jolla Cancer Research Foundationreporting that decorin binding to transforming growth factors hasinvolvement in a treatment for cancer, wound healing and scarring.Related by function to this group of proteins is the insulin like growthfactor (IGF), in that it is useful in wound-healing and associatedtherapies concerned with re-growth of tissue, such as connective tissue,skin and bone; in promoting body growth in humans and animals; and instimulating other growth-related processes. The acid labile subunit ofIGF (ALS) is also of interest in that it increases the half-life of IGFand is part of the IGF complex in vivo.

Another protein which has been reported to have leucine-rich repeats isthe SLIT protein which has been reported to be useful in treatingneuro-degenerative diseases such as Alzheimer's disease, nerve damagesuch as in Parkinson's disease, and for diagnosis of cancer, see,Artavanistsakonas, S. and Rothberg, J. M., WO9210518-A1 by YaleUniversity. Of particular interest is LIG-1, a membrane glycoproteinthat is expressed specifically in glial cells in the mouse brain, andhas leucine rich repeats and immunoglobulin-like domains. Suzuki, etal., J. Biol. Chem. (U.S.), 271(37):22522 (1996). Other studiesreporting on the biological functions of proteins having leucine richrepeats include: Tayar, N., et al., Moll. Cell Endocrinol., (Ireland),125(1–2):65–70 (December 1996) (gonadotropin receptor involvement);Miura, Y., et al., Nippon Rinsho (Japan), 54(7):1784–1789 (July 1996)(apoptosis involvement); Harris, P. C., et al., J. Am. Soc. Nephrol.,6(4):1125–1133 (October 1995) (kidney disease involvement).

We herein describe the identification and characterization of novelpolypeptides having homology to LIG, designated herein as PRO1111polypeptides.

65. PRO1344

Factor C is a protein that is intimately involved with the coagulationcascade in a variety of organisms. The coagulation cascade has beenshown to involve numerous different intermediate proteins, includingfactor C, all of whose activity is essential to the proper functioningof this cascade. Abnormal coagulation cascade function can result in avariety of serious abnormalities and, as such, the activities of thecoagulation cascade proteins is of particular interest. As such, effortsare currently being undertaken to identify novel polypeptides havinghomology to one or more of the coagulation cascade proteins.

We herein describe the identification and characterization of novelpolypeptides having homology to factor C protein, designated herein asPRO1344 polypeptides.

66. PRO1109

Carbohydrate chains on glycoproteins are important not only for proteinconformation, transport and stability, but also for cell-cell andcell-matrix interactions. β-1,4-galactosyltransferase is an enzyme thatis involved in producing carbohydrate chains on proteins, wherein theβ-1,4-galactosyltransferase enzyme acts to transfer galactose to theterminal N-acetylglucosamine of complex-type N-glycans in the Golgiapparatus (Asano et al., EMBO J. 16:1850–1857 (1997)). In addition, ithas been suggested that β-1,4-galactosyltransferase is involved directlyin cell-cell interactions during fertilization and early embryogenesisthrough a subpopulation of this enzyme distributed on the cell surface.Specifically, Lu et al., Development 124:4121–4131 (1997) and Larson etal., Biol. Reprod. 57:442–453 (1997) have demonstrated thatβ-1,4-galactosyltransferase is expressed on the surface of sperm from avariety of mammalian species, thereby suggesting an important role infertilization. In light of the above, novel polypeptides having sequenceidentity to β-1,4-galactosyltransferase are of interest.

We herein describe the identification and characterization of novelpolypeptides having homology to β-1,4-galactosyltransferase, designatedherein as PRO1109 polypeptides.

67. PRO1383

The nmb gene is a novel gene that encodes a putative transmembraneglycoprotein which is differentially expressed in metastatic humanmelanoma cell lines and which shows substantial homology to theprecursor of pMEL17, a melanocyte-specific protein (Weterman et al.,Int. J. Cancer 60:73–81 (1995)). Given the interest in identifyingtumor-specific cell-surface polypeptide markers, there is substantialinterest in novel polypeptides having homology to nmb. We hereindescribe the identification and characterization of novel polypeptideshaving homology to the nmb protein, designated herein as PRO1383polypeptides.

68. PRO1003

Efforts are being undertaken by both industry and academia to identifynew, native secreted proteins. Many of these efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel secreted proteins. We herein describe theidentification and characterization of novel secreted polypeptides,designated herein as PRO1003 polypeptides.

69. PRO1108

Lysophosphatidic acid acyltransferase (LPAAT) is an enzyme that in lipidmetabolism converts lysophosphatidic acid (LPA) into phosphatidic acid(PA). LPA is a phospholipid that acts as an intermediate in membranephospholipid metabolism. Various LPAAT enzymes have been identified in avariety of species (see, e.g., Aguado et al., J. Biol. Chem.273:4096–4105 (1998), Stamps et al., Biochem. J. 326:455–461 (1997),Eberhart et al., J. Biol. Chem. 272:20299–20305 (1997) and West et al.,DNA Cell Biol. 16:691–701 (1997)). Given the obvious importance of LPAATin a variety of different applications including cell membranemaintenance, there is substantial interest in identifying andcharacterizing novel polypeptides having homology to LPAAT. We hereindescribe the identification and characterization of novel polypeptideshaving homology to LPAAT protein, designated herein as PRO1108polypeptides.

70. PRO1137

A particular class of secreted polypeptides that are of interest inresearch and industry are ribosyltransferases. Braren et al. describedthe use of EST databases for the identification and cloning of novelribosyltransferase gene family members (Adv. Exp. Med. Biol. 419:163–168(1997)). Ribosyltransferases have been identified playing roles in avariety of metabolic functions including posttranslational modificationof proteins (Saxty et al., J. Leukoc. Biol., 63(1):15–21 (1998)), andmediation of the assembly of filamentous actin and chemotaxis inpolymorphonuclear neutrophil leukocytes (Kefalas et al. Adv. Exp. Med.Biol. 419:241–244 (1997)).

Described herein is the identification and characterization of novelpolypeptides having homology to ribosyltransferase, designated herein asPRO1137 polypeptides.

71. PRO1138

Efforts are being undertaken by both industry and academia to identifynew, native receptor proteins. Many efforts are focused on the screeningof mammalian recombinant DNA libraries to identify the coding sequencesfor novel receptor proteins. Of particular interest is theidentification of membrane-bound proteins found in cells of thehematopoietic system, as they often play important roles in fightinginfection, repair of injured tissues, and other activities of cells ofthe hematopoietic system. For instance, CD84 leukocyte antigen hasrecently been identified as a new member of the Ig superfamily (de laFuente et al., Blood, 90(6):2398–2405 (1997)).

Described herein is the identification and characterization of a novelpolypeptide having homology to CD84 leukocyte antigen, designated hereinas PRO1138 polypeptides.

72. PRO1054

The proteins of the major urinary protein complex (MUP), proteins whichare members of the lipocalin family, function to bind to volatilepheromones and interact with the vomeronasal neuroepithelium of theolfactory system. As such, proteins in the MUP family are intimatelyinvolved in the process of attraction between mammals of differentsexes. Many different MUP family members have been identified andcharacterized and shown to possess varying degrees of amino acidsequence homology (see, e.g., Mucignat et al., Chem. Senses 23:67–70(1998), Ferrari et al., FEBS Lett. 401:73–77 (1997) and Bishop et al.,EMBO J. 1:615–620 (1982)). Given the physiological and biologicalimportance of the MUP family of proteins, there is significant interestin identifying and characterizing novel members of this family. Weherein describe the identification and characterization of novelpolypeptides having homology to MUP family of proteins, designatedherein as PRO1054 polypeptides.

73. PRO994

The L6 cell surface antigen, which is highly expressed on lung, breast,colon, and ovarian carcinomas, has attracted attention as a potentialtherapeutic target for murine monoclonal antibodies and their humanizedcounterparts (Marken et al., Proc. Natl. Acad. Sci. USA 89:3503–3507(1992)). The cDNA encoding this tumor-associated cell surface antigenhas been expressed in COS cells and shown to encode a 202 amino acidpolypeptide having three transmembrane domains. The L6 antigen has beenshown to be related to a number of cell surface proteins that have beenimplicated in the regulation of cell growth, including for example CD63and CO-029, proteins which are also highly expressed on tumor cells. Assuch, there is significant interest in identifying novel polypeptideshaving homology to the L6 tumor cell antigen as potential targets forcancer therapy. We herein describe the identification andcharacterization of novel polypeptides having homology to the L6 cellsurface tumor cell-associated antigen, designated herein as PRO994polypeptides.

74. PRO812

Steroid binding proteins play important roles in numerous physiologicalprocesses associated with steroid function. Specifically, one steroidbinding protein-associated polypeptide that has been well characterizedis component 1 of the prostatic binding protein. Component 1 of theprostatic binding protein has been shown to be specific for subunit F ofthe prostatic binding protein, the major secretory glycoprotein of therat ventral prostate (Peeters et al., Eur. J. Biochem. 123:55–62 (1982)and Liao et al., J. Biol. Chem. 257:122–125 (1982)). The amino acidsequence of component I of the prostatic binding protein has beendetermined, wherein the sequence is highly rich in glutamic acidresidues and is overall highly acidic. This protein plays an importantrole in the response of the prostate gland to steroid hormones. Weherein describe the identification and characterization of novelpolypeptides having homology to prostatic steroid-binding protein c1,designated herein as PRO812 polypeptides.

75. PRO1069

Of particular interest is the identification of new membrane-boundproteins involved in ion conductance such as channel inhibitory factor(CHIF) and MAT-8, which have recently been reported (see Wald et al.,Am. J. Physiol, 272(5 pt 2): F617–F623 (1997); Capurro et al., Am. J.Physiol, 271(3 pt 1): C753–C762 (1996); Wald et al., Am. J. Physiol,271(2 pt 2): F322–F329 (1996); and Morrison et al., J. Biol. Chem270(5):2176–2182 (1995)).

Described herein is the identification and characterization of novelpolypeptides having homology to CHIF and MAT-8 polypeptides, designatedherein as PRO1069 polypeptides.

76. PRO1129

Cytochromes P-450 are a superfamily of hemoproteins which represent themain pathway for drug and chemical oxidation (Horsmans, ActaGastroenterol. Belg. 60:2–10 (1997)). This superfamily is divided intofamilies, subfamilies and/or single enzymes. Recent reports haveprovided a great deal of information concerning the cytochrome P450isozymes and increased awareness of life threatening interactions withsuch commonly prescribed drugs as cisapride and some antihistamines(Michalets, Pharmacotherapy 18:84–112 (1998) and Singer et al., J. Am.Acad. Dermatol. 37:765–771 (1997)). Given this information, there issignificant interest in identifying novel members of the cytochromeP-450 family of proteins. We herein describe the identification andcharacterization of novel polypeptides having homology to cytochromeP-450 proteins, designated herein as PRO1129 polypeptides.

77. PRO1068

Urotensins are neurosecretory proteins that are of interest because oftheir potential roles in a variety of physiological processes includingsmooth muscle contraction (Yano et al. Gen. Comp. Endocrinol. 96(3):412–413 (1994)), regulation of arterial blood pressure and heart rate(Le Mevel et al. Am. J. Physiol. 271(5 Pt 2):R1335–R1343 (1996)), andcorticosteroid secretion (Feuilloley et al. J. Steroid Biochem Mol.Biol. 48(2–3): 287–292 (1994)).

We herein describe the identification and characterization of novelpolypeptides having homology to urotensin, designated herein as PRO1068polypeptides.

78. PRO1066

Efforts are being undertaken by both industry and academia to identifynew, native secreted proteins. Many of these efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel secreted proteins. We herein describe theidentification and characterization of novel secreted polypeptides,designated herein as PRO1066 polypeptides.

79. PRO1184

Efforts are being undertaken by both industry and academia to identifynew, native secreted proteins. Many of these efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel secreted proteins. We herein describe theidentification and characterization of novel secreted polypeptides,designated herein as PRO1184 polypeptides.

80. PRO1360

Efforts are being undertaken by both industry and academia to identifynew, native secreted proteins. Many of these efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel secreted proteins. We herein describe theidentification and characterization of novel secreted polypeptides,designated herein as PRO1360 polypeptides.

81. PRO1029

Efforts are being undertaken by both industry and academia to identifynew, native secreted proteins. Many of these efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel secreted proteins. We herein describe theidentification and characterization of novel secreted polypeptides,designated herein as PRO1029 polypeptides.

82. PRO1139

Obesity is the most common nutritional disorder which, according torecent epidemiologic studies, affects about one third of all Americans20 years of age or older. Kuczmarski et al., J. Am. Med. Assoc. 272,205–11 (1994). Obesity is responsible for a variety of serious healthproblems, including cardiovascular disorders, type II diabetes,insulin-resistance, hypertension, hypertriglyceridemia,dyslipoproteinemia, and some forms of cancer. Pi-Sunyer, F. X., Anns.Int. Med. 119, 655–60 (1993); Colfitz, G. A., Am. J. Clin. Nutr. 55,503S–507S (1992). A single-gene mutation (the obesity or “ob” mutation)has been shown to result in obesity and type II diabetes in mice.Friedman, Genomics 11, 1054–1062 (1991). Zhang et al., Nature 372,425–431 (1994) have recently reported the cloning and sequencing of themouse ob gene and its human homologue, and suggested that the ob geneproduct may function as part of a signaling pathway from adipose tissuethat acts to regulate the size of the body fat depot. Parabiosisexperiments performed more than 20 years ago predicted that thegenetically obese mouse containing two mutant copies of the ob gene(ob/ob mouse) does not produce a satiety factor which regulates its foodintake, while the diabetic (db/db) mouse produces but does not respondto a satiety factor. Coleman and Hummal, Am. J. Physiol. 217, 1298–1304(1969); Coleman, Diabetol. 9, 294–98 (1973). OB proteins are disclosed,for example, in U.S. Pat. Nos. 5,532,336; 5,552,522; 5,552,523;5,552,514; 5,554,727. Recent reports by three independent research teamshave demonstrated that daily injections of recombinant OB proteininhibit food intake and reduce body weight and fat in grossly obeseob/ob mice but not in db/db mice (Pelleymounter et al., Science 269,540–43 [1995]; Halaas et al., Science 269, 543–46 [1995]; Campfield etal., Science 269, 546–49 [1995]), suggesting that the ob protein is sucha satiety factor as proposed in early cross-circulation studies.

A receptor of the OB protein (OB-R) is disclosed in Tartaglia et al.,Cell 83, 1263–71 (1995). The OB-R is a single membrane-spanning receptorhomologous to members of the class I cytokine receptor family (Tartagliaet al., supra; Bazan, Proc. Natl. Acad. Sci. USA 87, 6934–6938 [1990]).Two 5′-untranslated regions and several 3′-alternative splice variantsencoding OB-R with cytoplasmic domains of different lengths have beendescribed in mouse, rat and human (Chen et al., Cell 84, 491–495 [1996];Chua et al., Science 271, 994–996 [1996]; Tartaglia et al., supra; Wanget al., FEBS Lett. 392:87–90 [1996]; Phillips et al., Nature Genet. 13,18–19 [1996]; Cioffi et al., Nature Med., 2 585–589 [1996]). A humanhematopoetin receptor, which might be a receptor of the OB protein, isdescribed in PCT application Publication No. WO 96/08510, published Mar.21, 1996.

Bailleul et al., Nucl. Acids Res. 25, 2752–2758 (1997) identified ahuman mRNA splice variant of the OB-R gene that potentially encodes anovel protein, designated as leptin receptor gene-related protein(OB-RGRP). This protein displays no sequence similarity to the leptinreceptor itself. The authors found that the OB-RGRP gene shares itspromoter and two exons with the OB-R gene, and suggested that there is arequirement for a coordinate expression of OB-R and OB-RGRP to elicitthe full physiological response to leptin in vivo.

83. PRO1309

Protein-protein interactions include receptor and antigen complexes andsignaling mechanisms. As more is known about the structural andfunctional mechanisms underlying protein-protein interactions,protein-protein interactions can be more easily manipulated to regulatethe particular result of the protein-protein interaction. Thus, theunderlying mechanisms of protein-protein interactions are of interest tothe scientific and medical community.

All proteins containing leucine-rich repeats are thought to be involvedin protein-protein interactions. Leucine-rich repeats are short sequencemotifs present in a number of proteins with diverse functions andcellular locations. The crystal structure of ribonuclease inhibitorprotein has revealed that leucine-rich repeats correspond to beta-alphastructural units. These units are arranged so that they form a parallelbeta-sheet with one surface exposed to solvent, so that the proteinacquires an unusual, nonglubular shape. These two features have beenindicated as responsible for the protein-binding functions of proteinscontaining leucine-rich repeats. See, Kobe and Deisenhofer, TrendsBiochem. Sci., 19(10):415–421 (October 1994); Kobe and Deisenhofer,Curr. Opin. Struct. Biol., 5(3):409–416 (1995).

A study has been reported on leucine-rich proteoglycans which serve astissue organizers, orienting and ordering collagen fibrils duringontogeny and are involved in pathological processes such as woundhealing, tissue repair, and tumor stroma formation. Iozzo, R. V., Crit.Rev. Biochem. Mol. Biol., 32(2):141–174 (1997). Others studiesimplicating leucine rich proteins in wound healing and tissue repair areDe La Salle, C., et al., Vouv. Rev. Fr. Hematol. (Germany),37(4):215–222 (1995), reporting mutations in the leucine rich motif in acomplex associated with the bleeding disorder Bernard-Soulier syndrome,Chlemetson, K. J., Thromb. Haemost. (Germany), 74(1):111–116 (July1995), reporting that platelets have leucine rich repeats and Ruoslahti,E. I., et al., WO9110727-A by La Jolla Cancer Research Foundationreporting that decorin binding to transforming growth factors hasinvolvement in a treatment for cancer, wound healing and scarring.Related by function to this group of proteins is the insulin like growthfactor (IGF), in that it is useful in wound-healing and associatedtherapies concerned with re-growth of tissue, such as connective tissue,skin and bone; in promoting body growth in humans and animals; and instimulating other growth-related processes. The acid labile subunit ofIGF (ALS) is also of interest in that it increases the half-life of IGFand is part of the IGF complex in vivo.

Another protein which has been reported to have leucine-rich repeats isthe SLIT protein which has been reported to be useful in treatingneuro-degenerative diseases such as Alzheimer's disease, nerve damagesuch as in Parkinson's disease, and for diagnosis of cancer, see,Artavanistsakonas, S. and Rothberg, J. M., WO9210518-A1 by YaleUniversity. Of particular interest is LIG-1, a membrane glycoproteinthat is expressed specifically in glial cells in the mouse brain, andhas leucine rich repeats and immunoglobulin-like domains. Suzuki, etal., J. Biol. Chem. (U.S.), 271(37):22522 (1996). Other studiesreporting on the biological functions of proteins having leucine richrepeats include: Tayar, N., et al., Moll. Cell Endocrinol., (Ireland),125(1–2):65–70 (December 1996) (gonadotropin receptor involvement);Miura, Y., et al., Nippon Rinsho (Japan), 54(7):1784–1789 (July 1996)(apoptosis involvement); Harris, P. C., et al., J. Am. Soc. Nephrol.,6(4):1125–1133 (October 1995) (kidney disease involvement).

Efforts are therefore being undertaken by both industry and academia toidentify new proteins having leucine rich repeats to better understandprotein-protein interactions. Of particular interest are those proteinshaving leucine rich repeats and homology to known proteins havingleucine rich repeats such as platelet glycoprotein V, SLIT and ALS. Manyefforts are focused on the screening of mammalian recombinant DNAlibraries to identify the coding sequences for novel membrane-boundproteins having leucine rich repeats.

84. PRO1028

Efforts are being undertaken by both industry and academia to identifynew, native secreted proteins. Many of these efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel secreted proteins. We herein describe theidentification and characterization of novel secreted polypeptides,designated herein as PRO1028 polypeptides.

85. PRO1027

Efforts are being undertaken by both industry and academia to identifynew, native secreted proteins. Many of these efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel secreted proteins. We herein describe theidentification and characterization of novel secreted polypeptides,designated herein as PRO1027 polypeptides.

86. PRO1107

Of particular interest are novel proteins having some sequence identityto known proteins. Known proteins include PC-1, an ecto-enzymepossessing alkaline phosphodiesterase I and nucleotide pyrophosphataseactivities, further described in Belli et al., Eur. J. Biochem.,228(3):669–676 (1995). Phosphodiesterases are also described in Fuss etal., J. Neurosci., 17(23):9095–9103 (1997) and Scott et al., Hepatology,25(4):995–1002 (1997). Phosphodiesterase I, is described as a noveladhesin molecule and/or cytokine (related to autotaxin) involved inoligodendrocyte function. Fuss, supra.

We herein describe the identification and characterization of novelpolypeptides having homology into PC-1, designated herein as PRO1107polypeptides.

87. PRO1140

Efforts are being undertaken by both industry and academia to identifynew, native membrane-bound proteins. Many of these efforts are focusedon the screening of mammalian recombinant DNA libraries to identify thecoding sequences for novel membrane-bound proteins. We herein describethe identification and characterization of novel transmembranepolypeptides, designated herein as PRO1140 polypeptides.

88. PRO1106

As the mitochondria is primarily responsible for generating energy,proteins associated with the mitochondria are of interest. Recently, acDNA from a novel Ca⁺⁺-dependent member of the mitochondrial solutecarrier superfamily was isolated from a rabbit small intestinal cDNAlibrary as described in Weber, et al., PNAS USA, 94(16):8509–8514(1997). It was reported that this transporter has four elongationfactor-hand motifs in the N-terminal and is localized in the peroxisome,although a fraction can be found in the mitochondria. Thus, thistransporter, and proteins which have sequence identity to this and othermembers of the mitochondrial solute carrier superfamily are ofparticular interest.

We herein describe the identification and characterization of novelpolypeptides having homology to a peroxisomal calcium dependent solutecarrier protein, designated herein as PRO1106 polypeptides.

89. PRO1291

Butyrophilin is a milk glycoprotein that constitutes more than 40% ofthe total protein associated with the fat globule membrane in mammalianmilk. Expression of butyrophilin mRNA has been shown to correlate withthe onset of milk fat production toward the end pregnancy and ismaintained throughout lactation. Butyrophilin has been identified inbovine, murine and human (see Taylor et al., Biochim. Biophys. Acta1306:1–4 (1996), Ishii et al., Biochim. Biophys. Acta 1245:285–292(1995), Mather et al., J. Dairy Sci. 76:3832–3850 (1993) and Banghart etal., J. Biol. Chem. 273:4171–4179 (1998)) and is a type I transmembraneprotein that is incorporated into the fat globulin membrane. It has beensuggested that butyrophilin may play a role as the principle scaffoldfor the assembly of a complex with xanthine dehydrogenaseloxidase andother proteins that function in the budding and release of milk-fatglobules from the apical surface during lactation (Banghart et al.,supra).

Given that butyrophilin plays an obviously important role in mammalianmilk production, there is substantial interest in identifying novelbutyrophilin homologs. We herein describe the identification andcharacterization of novel polypeptides having homology to butyrophilin,designated herein as PRO1291 polypeptides.

90. PRO1105

Efforts are being undertaken by both industry and academia to identifynew, native membrane-bound proteins. Many of these efforts are focusedon the screening of mammalian recombinant DNA libraries to identify thecoding sequences for novel membrane-bound proteins. We herein describethe identification and characterization of novel transmembranepolypeptides, designated herein as PRO1105 polypeptides.

91. PRO511

Proteins of interest include those having sequence identity with RoBo-1,a novel member of the urokinase plasminogen activatorreceptor/CD59/Ly-6/snake toxin family selectively expressed in bone andgrowth plate cartilage as described in Noel et al., J. Biol. Chem.273(7):3878–3883 (1998). RoBo-1 is believed to play a novel role in thegrowth or remodeling of bone. Proteins also of interest include thosehaving sequence identity with phospholipase inhibitors.

We herein describe the identification and characterization of novelpolypeptides having homology to urokinase plasminogen activatorreceptors and phospholipase inhibitors, designated herein as PRO511polypeptides.

92. PRO1104

Efforts are being undertaken by both industry and academia to identifynew, native secreted proteins. Many of these efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel secreted proteins. We herein describe theidentification and characterization of novel secreted polypeptides,designated herein as PRO1104 polypeptides.

93. PRO1100

Efforts are being undertaken by both industry and academia to identifynew, native membrane-bound proteins. Many of these efforts are focusedon the screening of mammalian recombinant DNA libraries to identify thecoding sequences for novel membrane-bound proteins. We herein describethe identification and characterization of novel transmembranepolypeptides, designated herein as PRO1100 polypeptides.

94. PRO836

Of interest are luminal proteins, or proteins specific to theendoplasmic reticulum (ER). Of particular interest are proteins havingsequence identity with known proteins. Known proteins include proteinssuch as SLS1. In Saccharomyces cerevisiae, SLS1 has been reported to bea mitochondrial integral membrane protein involved in mitochondrialmetabolism. Rouillard, et al., Mol. Gen. Genet., 252(6):700–708 (1996).In yeast Yarrowia lipolytica, it has been reported that the SLS1 geneproduct (SLS1p) behaves as a lumenal protein of the ER. It is believedthat SPS1p acts in the preprotein translocation process, interactingdirectly with translocating polypeptides to facilitate their transferand/or help their folding in the ER. Bosirarne, et al., J. Biol. Chem.,271(20):11668–11675 (1996).

We herein describe the identification and characterization of novelpolypeptides having homology to SLS1, designated herein as PRO836polypeptides.

95. PRO1141

Efforts are being undertaken by both industry and academia to identifynew, native membrane-bound proteins. Many of these efforts are focusedon the screening of mammalian recombinant DNA libraries to identify thecoding sequences for novel membrane-bound proteins. We herein describethe identification and characterization of novel transmembranepolypeptides, designated herein as PRO1141 polypeptides.

396. PRO1132

Proteases are enzymatic proteins which are involved in a large number ofvery important biological processes in mammalian and non-mammalianorganisms. Numerous different protease enzymes from a variety ofdifferent mammalian and non-ammalian organisms have been both identifiedand characterized, including the serine proteases which exhibit specificactivity toward various serine-containing proteins. The mammalianprotease enzymes play important roles in biological processes such as,for example, protein digestion, activation, inactivation, or modulationof peptide hormone activity, and alteration of the physical propertiesof proteins and enzymes.

Neuropsin is a novel serine protease whose mRNA is expressed in thecentral nervous system. Mouse neuropsin has been cloned, and studieshave shown that it is involved in the hippocampal plasticity. Neuropsinhas also been indicated as associated with extracellular matrixmodifications and cell migrations. See, generally, Chen, et al.,Neurosci., 7(2):5088–5097 (1995) and Chen, et al., J. Histochem.Cytochem., 46:313–320 (1998).

Another serine protease of interest is the enamel matrix serineproteinase. The maturation of dental enamel succeeds the degradation oforganic matrix. Inhibition studies have shown that this degradation isaccomplished by a serine-type proteinase. Proteases associated withenamel maturation are described in, i.e., Simmer, et al., J. Dent. Res.,77(2):377–386 (1998), Overall and Limeback, Biochem J., 256(3):965–972(1988), and Moradian-Oldak, Connect. Tissue Res., 35(1–4):231–238(1996).

We herein describe the identification and characterization of novelpolypeptides having homology to serine proteases, designated herein asPRO1132 polypeptides.

97. PRO1346

The abbreviations “TIE” or “tie” are acronyms, which stand for “tyrosinekinase containing Ig and EGF homology domains” and were coined todesignate a new family of receptor tyrosine kinases which are almostexclusively expressed in vascular endothelial cells and earlyhemopoietic cells, and are characterized by the presence of an EGF-likedomain, and extracellular folding units stabilized by intra-chaindisulfide bonds, generally referred to as “immunoglobulin (IG)-like”folds. A tyrosine kinase homologous cDNA fragment from human leukemiacells (tie) was described by Partanen et al., Proc. Natl. Acad. Sci. USA87, 8913–8917 (1990). The mRNA of this human “TIE” receptor has beendetected in all human fetal and mouse embryonic tissues, and has beenreported to be localized in the cardiac and vascular endothelial cells.Korhonen et al., Blood 80, 2548–2555 (1992); PCT Application PublicationNo. WO 93/14124 (published 22, Jul. 1993). The rat homolog of human TIE,referred to as “TIE-1”, was identified by Maisonpierre et al., Oncogene8, 1631–637 (1993)). Another TIE receptor, designated “TIE-2” wasoriginally identified in rats (Dumont et al., Oncogene 8, 1293–1301(1993)), while the human homolog of TIE-2, referred to as “ork” wasdescribed in U.S. Pat. No. 5,447,860 (Ziegler). The murine homolog ofTIE-2 was originally termed “tek.” The cloning of a mouse TIE-2 receptorfrom a brain capillary cDNA library is disclosed in PCT ApplicationPublication No. WO 95/13387 (published 18, May 1995). TIE-2 is areceptor tyrosine kinase that is expressed almost exclusively byvascular endothelium. Tie-2 knockout mice die by defects in theformation of microvassels. Accordingly, the TIE receptors are believedto be actively involved in angiogenesis, and may play a role inhemopoiesis as well. Indeed, recent results (Lin et al., J. Clin.Invest. 100(8), 2072–2078 [1997]) demonstrating the ability of a solubleTIE-2 receptor to inhibit tumor angiogenesis have been interpreted toindicate that TIE-2 plays a role in pathologic vascular growth. Inanother study, TIE-2 expression was examined in adult tissues undergoingangiogenesis and in quiescent tissues. TIE2 expression was localized byimmunohistochemistry to the endothelium of neovessels in rat tissuesundergoing angiogenesis during hormonally stimulated follicularmaturation and uterine development and in healing wounds. TIE-2 was alsoreported to be expressed in the entire spectrum of the quiescentvasculature (arteries, veins, and capillaries) in a wide range of adulttissues. Wong et al., Circ. Res. 81(4), 567–574 (1997). It has beensuggested that TIE-2 has a dual function in adult angiogenesis andvascular maintenance.

The expression cloning of human TIE-2 ligands has been described in PCTApplication Publication No. WO 96/11269 (published 18, Apr. 1996) and inU.S. Pat. No. 5,521,073 (published 28, May 1996). A vector designated asλgt10 encoding a TIE-2 ligand NL7d “htie-2 ligand 1” or “hTL1” has beendeposited under ATCC Accession No. 75928. A plasmid encoding anotherTIE-2 ligand designated “htie-2 2” or “hTL2” is available under ATCCAccession No. 75928. This second ligand has been described as anantagonist of the TAI-2 receptor. The identification of secreted humanand mouse ligands for the TIE-2 receptor has been reported by Davis etal., Cell 87, 1161–1169 (1996). The human ligand designated“Angiopoietin-1”, to reflect its role in angiogenesis and potentialaction during hemopoiesis, is the same ligand as the ligand variouslydesignated as “htie-2 1” or “hTL-1” in WO 96/11269. Angiopoietin-1 hasbeen described to play an angiogenic role later and distinct from thatof VEGF (Suri et al., Cell 87, 1171–1180 (1996)). Since TIE-2 isapparently upregulated during the pathologic angiogenesis requisite fortumor growth (Kaipainen et al., Cancer Res. 54, 6571–6577 (1994))angiopoietin-1 has been suggested to be additionally useful forspecifically targeting tumor vasculature (Davis et al., supra).

We herein describe the identification and characterization of novel TIEligand polypeptides, designated herein as PRO1346 polypeptides.

98. PRO1131

The low density lipoprotein (LDL) receptor is a membrane-bound proteinthat plays a key role in cholesterol homeostasis, mediating cellularuptake of lipoprotein particles by high affinity binding to its ligands,apolipoprotein (apo) B-100 and apoE. The ligand-binding domain of theLDL receptor contains 7 cysteine-rich repeats of approximately 40 aminoacids, wherein each repeat contains 6 cysteines, which form 3intra-repeat disulfide bonds. These unique structural features providethe LDL receptor with its ability to specifically interact with apoB-100 and apoE, thereby allowing for transport of these lipoproteinparticles across cellular membranes and metabolism of their components.Soluble fragments containing the extracellular domain of the LDLreceptor have been shown to retain the ability to interact with itsspecific lipoprotein ligands (Simmons et al., J. Biol. Chem.272:25531–25536 (1997)). LDL receptors are further described in Javitt,FASEB J., 9(13): 1378–1381 (1995), van Berkel, et al., Atherosclerosis,118 Suppl:S43–S50 (1995) and Herz and Willnow, Ann. NY Acad. Sci.,737:14–19 (1994). Thus, proteins having sequence identity with LDLreceptors are of interest.

We herein describe the identification and characterization of novelpolypeptides having homology to LDL receptors, designated herein asPRO1131 polypeptides.

99. PRO1281

Efforts are being undertaken by both industry and academia to identifynew, native secreted proteins. Many of these efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel secreted proteins. We herein describe theidentification and characterization of novel secreted polypeptides,designated herein as PRO1281 polypeptides.

100. PRO1064

Efforts are being undertaken by both industry and academia to identifynew, native membrane-bound proteins. Many of these efforts are focusedon the screening of mammalian recombinant DNA libraries to identify thecoding sequences for novel membrane-bound proteins. We herein describethe identification and characterization of novel transmembranepolypeptides, designated herein as PRO1064 polypeptides.

101. PRO1379

Efforts are being undertaken by both industry and academia to identifynew, native secreted proteins. Many of these efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel secreted proteins. We herein describe theidentification and characterization of novel secreted polypeptides,designated herein as PRO1379 polypeptides.

102. PRO844

Proteases are enzymatic proteins which are involved in a large number ofvery important biological processes in mammalian and non-mammalianorganisms. Numerous different protease enzymes from a variety ofdifferent mammalian and non-mammalian organisms have been bothidentified and characterized. The mammalian protease enzymes playimportant roles in many different biological processes including, forexample, protein digestion, activation, inactivation, or modulation ofpeptide hormone activity, and alteration of the physical properties ofproteins and enzymes. Thus, proteases are of interest. Also of interestare protease inhibitors.

Of particular interest are serine proteases. In one study it wasreported that when the serine protease inhibitor antileukoproteinase(aLP) is injected, it accumulates in articular and extraarticularcartilage of normal rats. This physiological pathway of cartilageaccumulation, lost in proteoglycan depleted arthritic cartilage isbelieved to serve to maintain the local balance between proteinasefunction and inhibition. Burkhardt, et al., J. Rheumatol,24(6):1145–1154 (1997). Moreover, aLP and other protease inhibitors havebeen reported to play a role in the in vitro growth of hematopoietccells by the neutralization of proteinases produced by bone marrowaccessory cells. Gosklink, et al., J. Exp. Med., 184(4):1305–1312(1996). Also of interest are mutants of aLP. Oxidation resistant mutantsof aLPe have been reported to have significant therapeutic effects onanimal models having emphysema. Steffens, et al., Agents Actions Suppl.,42:111–121 (1993). Thus, serine protease inhibitors are of interest.

We herein describe the identification and characterization of novelpolypeptides having homology to serine protease inhibitors, designatedherein as PRO844 polypeptides.

103. PRO848

Membrane-bound proteins of interest include channels such as ionchannels. Furthermore, membrane-bound proteins of interest includeenzymes bound to intracellular vacuoles or organelles, such astransferases. For example, a peptide of interest is the GalNAc alpha 2,6-sailytransferase as described in Kurosawa, et al., J. Biol. Chem.,269(2):1402–1409 (1994). This peptide was constructed to be secreted,and retained its catalytic activity. The expressed enzyme exhibitedactivity toward asialomucin and asialofetuin, but not otherglycoproteins tested. As sialylation is an important function,sialyltransferases such as this one, and peptides related by sequenceidentity, are of interest.

We herein describe the identification and characterization of novelpolypeptides having homology to sialyltransferases, designated herein asPRO848 polypeptides.

104. PRO1097

Efforts are being undertaken by both industry and academia to identifynew, native secreted proteins. Many of these efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel secreted proteins. We herein describe theidentification and characterization of novel secreted polypeptides,designated herein as PRO1097 polypeptides.

105. PRO1153

Efforts are being undertaken by both industry and academia to identifynew, native membrane-bound proteins. Many of these efforts are focusedon the screening of mammalian recombinant DNA libraries to identify thecoding sequences for novel transmembrane proteins. We herein describethe identification and characterization of novel transmembranepolypeptides, designated herein as PRO1153 polypeptides.

106. PRO1154

Aminopeptidase N causes enzymatic degradation of perorally administeredpeptide drugs. Thus, aminopeptidase N has been used in studies todevelop and identify inhibitors so as to increase the efficacy ofpeptide drugs by inhibiting their degradation. Aminopeptidases are alsogenerally of interest to use to degrade peptides. Aminopeptidases,particularly novel aminopeptidases are therefore of interest.Aminopeptidase N and inhibitors thereof are further described inBernkop-Schnurch and Marschutz, Pharm. Res., 14(2): 181–185 ((1997);Lerche, et al., Mamm. Genome, 7(9):712–713 (1996); Papapetropoulos, etal., Immunopharmacology, 32(1–3):153–156 (1996); Miyachi, et al., J.Med. Chem., 41(3):263–265 (1998); and Olsen, et al., Adv. Exp. Med.Biol., 421:47–57 (1997).

We herein describe the identification and characterization of novelpolypeptides having homology to aminopeptidase N, designated herein asPRO1154 polypeptides.

107. PRO1181

Efforts are being undertaken by both industry and academia to identifynew, native secreted proteins. Many of these efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel secreted proteins. We herein describe theidentification and characterization of novel secreted polypeptides,designated herein as PRO1181 polypeptides.

108. PRO1182

Conglutinin is a bovine serum protein that was originally described as avertebrate lectin protein and which belongs to the family of C-typelectins that have four characteristic domains, (1) an N-terminalcysteine-rich domain, (2) a collagen-like domain, (3) a neck domain and(4) a carbohydrate recognition domain (CRD). Recent reports havedemonstrated that bovine conglutinin can inhibit hemagglutination byinfluenza A viruses as a result of their lectin properties (Eda et al.,Biochem. J. 316:43–48 (1996)). It has also been suggested that lectinssuch as conglutinin can function as immunoglobulin-independent defensemolecules due to complement-mediated mechanisms. Thus, conglutinin hasbeen shown to be useful for purifying immune complexes in vitro and forremoving circulating immune complexes from patients plasma in vivo (Limet al., Biochem. Biophys. Res. Commun. 218:260–266 (1996)). We hereindescribe the identification and characterization of novel polypeptideshaving homology to conglutinin protein, designated herein as PRO1182polypeptides.

109. PRO1155

Substance P and the related proteins, neurokinin A and neurokinin B havebeen reported as compounds which elicit contraction of the ileum bothdirectly through action on a muscle cell receptor and indirectly throughstimulation of a neuronal receptor. This action leads to the release ofacetylcholine which causes muscle contraction via muscarinic receptors.It has also been reported that neurokinin B was found to be the mostpotent agonist for the neuronal Substance P receptor and that neurokininB can be inhibited by enkephalinamide. Laufer, et al., PNAS USA,82(21):74444–7448 (1985). Moreover, neurokinin B has been reported toprovide neuroprotection and cognitive enhancement, and thereforebelieved to be useful for the treatment of neurodegenerative disorders,including alzheimers disease. Wenk, et al., Behav. Brain Res.,83(1–2):129–133 (1997). Tachykinins are also described in Chawla, etal., J. Comp. Neurol., 384(3):429–442 (1997). Thus, tachykinins,particularly those related to neurokinin B are of interest.

We herein describe the identification and characterization of novelpolypeptides having homology to neurokinin B protein, designated hereinas PRO1155 polypeptides.

110. PRO1156

Efforts are being undertaken by both industry and academia to identifynew, native secreted proteins. Many of these efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel secreted proteins. We herein describe theidentification and characterization of novel secreted polypeptides,designated herein as PRO1181 polypeptides.

111. PRO1098

Efforts are being undertaken by both industry and academia to identifynew, native secreted proteins. Many of these efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel secreted proteins. We herein describe theidentification and characterization of novel secreted polypeptides,designated herein as PRO1098 polypeptides.

112. PRO1127

Efforts are being undertaken by both industry and academia to identifynew, native secreted proteins. Many of these efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel secreted proteins. We herein describe theidentification and characterization of novel secreted polypeptides,designated herein as PRO1127 polypeptides.

113. PRO1126

The extracellular mucous matrix of olfactory neuroepithelium is a highlyorganized structure in intimate contact with chemosensory cilia thathouse the olfactory transduction machinery. The major protein componentof this extracellular matrix is olfactomedin, a glycoprotein that isexpressed in olfactory neuroepithelium and which form intermoleculardisulfide bonds so as to produce a polymer (Yokoe et al., Proc. Natl.Acad. Sci. USA 90:4655–4659 (1993), Bal et al., Biochemistry32:1047–1053 (1993) and Snyder et al., Biochemistry 30:9143–9153(1991)). It has been suggested that olfactomedin may influence themaintenance, growth or differentiation of chemosensory cilia on theapical dendrites of olfactory neurons. Given this important role, thereis significant interest in identifying and characterizing novelpolypeptides having homology to olfactomedin. We herein describe theidentification and characterization of novel polypeptides havinghomology to olfactomedin protein, designated herein as PRO1126polypeptides.

114. PRO1125

Of particular interest are proteins which have multiple Trp-Asp (WD)repeats. WD proteins are made up of highly conserved repeating unitsusually ending with WD. They are found in eukaryotes but not inprokaryotes. They regulate cellular functions, such as cell division,cell-fate determination, gene transcription, gene transcription,transmembrane signaling, mRNA modification and vesicle fusion. WD arefurther described in Neer, et al., Nature, 371(6495):297–300 (1994);Jiang and Struhl, Nature, 391(6666):493–496(1998); and DeSilva, et al.,Genetics, 148(2):657–667 (1998). Thus, new members of this superfamilyare all of interest.

115. PRO1186

Protein A from Dendroaspis polylepis polylepis (black mamba) venomcomprises 81 amino acids, including ten half-cystine residues. Venomsare of interest on the one hand as weapons in war, and on the otherhand, to use in assays to determine agents which reverse or inhibit theeffects of the venom or a similar poison. Black mamba venom is furtherdescribed in Int. J. Biochem., 17(6):695–699 (1985) and Joubert andStrydom, Hoppe Seylers Z Physiol. Chem., 361(12):1787–1794 (1980).

We herein describe the identification and characterization of novelpolypeptides having homology to snake venom protein A, designated hereinas PRO1186 polypeptides.

116. PRO1198

Efforts are being undertaken by both industry and academia to identifynew, native secreted proteins. Many of these efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel secreted proteins. We herein describe theidentification and characterization of novel secreted polypeptides,designated herein as PRO1198 polypeptides.

117. PRO1158

Efforts are being undertaken by both industry and academia to identifynew, native membrane-bound proteins. Many of these efforts are focusedon the screening of mammalian recombinant DNA libraries to identify thecoding sequences for novel transmembrane proteins. We herein describethe identification and characterization of novel transmembranepolypeptides, designated herein as PRO1158 polypeptides.

118. PRO1159

Efforts are being undertaken by both industry and academia to identifynew, native secreted proteins. Many of these efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel secreted proteins. We herein describe theidentification and characterization of novel secreted polypeptides,designated herein as PRO1159 polypeptides.

119. PRO1124

Ion channels are considered to be the gateway to the final frontier, thebrain. Ion channels and the receptors which control these channels areresponsible for the passage of ions, or nerve impulses to becommunicated from cell to cell, thus, ion channels are responsible forcommunication. In addition to their critical role in the brain, ionchannels play a critical role in the heart as well as blood pressure.Ion channels have also been linked to other important bodily functionsand conditions, as well as disorders, such as cystic fibrosis. For allof these reasons, ion channels, such as sodium, potassium and chloridechannels, as well as all of their related proteins and receptors are ofinterest. For example, it has been reported that cystic fibrosis resultsfrom a defect in the chloride channel protein, cystic fibrosistransmembrane conductance regulator. McGill, et al., Dig. Dis. Sci.,41(3):540–542 (1996). Chloride channels are further described in atleast Finn, et al., PNAS USA, 90(12):5691–569 (1993) and Finn, et al.,Mol. Cell Biochem., 114(1–2):21–26 (1992).

Also of interest are molecules related to adhesion molecules, asadhesion molecules are known to be involved in cell-cell signaling andinteractions. More generally, all novel membrane bound-proteins are ofinterest. Membrane-bound proteins and receptors can play an importantrole in the formation, differentiation and maintenance of multicellularorganisms. The fate of many individual cells, e.g., proliferation,migration, differentiation, or interaction with other cells, istypically governed by information received from other cells and/or theimmediate environment. This information is often transmitted by secretedpolypeptides (for instance, mitogenic factors, survival factors,cytotoxic factors, differentiation factors, neuropeptides, and hormones)which are, in turn, received and interpreted by diverse cell receptorsor membrane-bound proteins. Such membrane-bound proteins and cellreceptors include, but are not limited to, cytokine receptors, receptorkinases, receptor phosphatases, receptors involved in cell-cellinteractions, channels, transporters, and cellular adhesin moleculeslike selectins and integrins. For instance, transduction of signals thatregulate cell growth and differentiation is regulated in part byphosphorylation of various cellular proteins. Protein tyrosine kinases,enzymes that catalyze that process, can also act as growth factorreceptors. Examples include fibroblast growth factor receptor and nervegrowth factor receptor.

Membrane-bound proteins include those which are bound to the outermembrane and intracellular membranes and organelles. Membrane-boundproteins and receptor molecules have various industrial applications,including as pharmaceutical and diagnostic agents. Receptorimmunoadhesins, for instance, can be employed as therapeutic agents toblock receptor-ligand interaction. The membrane-bound proteins can alsobe employed for screening of potential peptide or small moleculeinhibitors of the relevant receptor/ligand interaction.

Efforts are being undertaken by both industry and academia to identifynew, native receptor proteins. Many efforts are focused on the screeningof mammalian recombinant DNA libraries to identify the coding sequencesfor novel receptor proteins. Herein is presented a polypeptide andnucleic acid encoding therefor which has sequence identity with achloride channel protein chloride channel protein and lung-endothelialcell adhesion molecule-1 (ECAM-1).

120. PRO1287

Fringe is a protein which specifically blocks serrate-mediatedactivation of notch in the dorsal compartment of the Drosophila wingimaginal disc. Fleming et al., Development, 124(15):2973–81 (1997).Therefore, fringe protein is of interest for both its role indevelopment as well as its ability to regulate serrate, particularlyserrate's signaling abilities. Also of interest are novel polypeptideswhich may have a role in development and/or the regulation ofserrate-like molecules. Of particular interest are novel polypeptideshaving homology to fringe.

We herein describe the identification and characterization of novelpolypeptides having homology to fringe protein, designated herein asPRO1287 polypeptides.

121. PRO1312

Efforts are being undertaken by both industry and academia to identifynew, native membrane-bound proteins. Many of these efforts are focusedon the screening of mammalian recombinant DNA libraries to identify thecoding sequences for novel transmembrane proteins. We herein describethe identification and characterization of novel transmembranepolypeptides, designated herein as PRO1312 polypeptides.

122. PRO1192

Membrane-bound proteins of myelin are of interest because of theirpossible implications in various nervous system disorders associatedwith improper myelination. Myelin is a cellular sheath, formed by glialcells, that surrounds axons and axonal processes that enhances variouselectrochemical properties and provides trophic support to the neuron.Myelin is formed by Schwann cells in the peripheral nervous system (PNS)and by oligodendrocytes in the central nervous system (CNS). Impropermyelination of central and peripheral neurons occurs in a number ofpathologies and leads to improper signal conduction within the nervoussystems. Among the various demyelinating diseases Multiple Sclerosis isthe most notable.

The predominant integral membrane protein of the CNS myelin ofamphibians, reptiles, birds and mammals are proteolipid protein (PLP)and P0, the main glycoprotein in PNS myelin. (Schlieess and Stoffel,Biol. Chem. Hoppe Seyler (1991) 372(9):865–874). In view of theimportance of membrane-bound proteins of the myelin, efforts are beingundertaken by both industry and academia to identify and characterizevarious myelin proteins (see Stratmann and Jeserich, J. Neurochem (1995)64(6):2427–2436).

123. PRO1160

Efforts are being undertaken by both industry and academia to identifynew, native secreted proteins. Many of these efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel secreted proteins. We herein describe theidentification and characterization of novel secreted polypeptides,designated herein as PRO1160 polypeptides.

124. PRO1187

Efforts are being undertaken by both industry and academia to identifynew, native secreted proteins. Many of these efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel secreted proteins. We herein describe theidentification and characterization of novel secreted polypeptides,designated herein as PRO1187 polypeptides.

125. PRO1185

Efforts are being undertaken by both industry and academia to identifynew, native secreted proteins. Many of these efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel secreted proteins. We herein describe theidentification and characterization of novel secreted polypeptides,designated herein as PRO1185 polypeptides.

126. PRO345

Human tetranectin is a 202 amino acid protein encoded by a gene spanningapproximately 12 kbp of DNA (Berglund et al., FEBS Lett. 309:15–19(1992)). Tetranectin has been shown to be expressed in a variety oftissues and functions primarily as a plasminogen binding protein.Tetranectin has been classified in a distinct group of the C-type lectinsuperfamily but has structural and possibly functional similarity to thecollectin proteins (Nielsen et al., FEBS Lett. 412(2):388–396 (1997)).Recent studies have reported that variability in serum tetranectinlevels may be predictive of the presence of various types of cancersincluding, for example, ovarian and colorectal cancers (Hogdall et al.,Acta Oncol. 35:63–69 (1996), Hogdall et al., Eur. J. Cancer31A(6):888–894 (1995) and Tuxen et al., Cancer Treat. Rev. 21(3):215–245(1995)). As such, there is significant interest in identifying andcharacterizing novel polypeptides having structural and functionalsimilarity to the tetranectin protein.

We herein describe the identification and characterization of novelpolypeptides having homology to tetranectin protein, designated hereinas PRO1345 polypeptides.

127. PRO1245

Efforts are being undertaken by both industry and academia to identifynew, native secreted proteins. Many of these efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel secreted proteins. We herein describe theidentification and characterization of novel secreted polypeptides,designated herein as PRO1245 polypeptides.

128. PRO358

Serine protease inhibitors are of interest because they inhibitcatabolism and are sometimes associated with regeneration of tissue. Forexample, a gene encoding a plasma protein associated with liverregeneration has been cloned and termed regeneration-associated serpin-1(RASP-1). New, et al., Biochem. Biophys. Res. Commun., 223(2):404–412(1996). While serine protease inhibitors are of interest, particularlyof interest are those which have sequence identity with known serineprotease inhibitors such as RASP-1.

We herein describe the identification and characterization of novelpolypeptides having homology to RASP-1, designated herein as PRO1245polypeptides.

129. PRO1195

Efforts are being undertaken by both industry and academia to identifynew, native secreted proteins. Many of these efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel secreted proteins. We herein describe theidentification and characterization of novel secreted polypeptides,designated herein as PRO1195 polypeptides.

130. PRO1270

The recognition of carbohydrates by lectins has been found to play animportant role in various aspects of eukaryotic physiology. A number ofdifferent animal and plant lectin families exist, but it is the calciumdependent, or type C, lectins that have recently garnered the mostattention. For example, the recognition of carbohydrate residues oneither endothelial cells or leukocytes by the selectin family of calciumdependent lectins has been found to be of profound importance to thetrafficking of leukocytes to inflammatory sites. Lasky, L., Ann. Rev.Biochem., 64 113–139 (1995). The biophysical analysis of these adhesiveinteractions has suggested that lectin-carbohydrate binding evolved inthis case to allow for the adhesion between leukocytes and theendothelium under the high shear conditions of the vasculature. Thus,the rapid on rates of carbohydrate recognition by such lectins allowsfor a hasty acquisition of ligand, a necessity under the high shear ofthe vascular flow. The physiological use of type C lectins in this caseis also supported by the relatively low affinities of theseinteractions, a requirement for the leukocyte rolling phenomenon thathas been observed to occur at sites of acute inflammation. The crystalstructures of the mannose binding protein (Weis et al., Science 254,1608–1615 [1991]; Weis et al., Nature 360 127–134 [1992]) and E-selectin(Graves et al., Nature 367(6463), 532–538 [1994]), together with variousmutagenesis analyses (Erbe et al., J. Cell. Biol. 119(1), 215–227[1992]; Drickamer, Nature 360, 183–186 [1992]; Iobst et al., J. Biol.Chem. 169(22), 15505–15511 [1994]; Kogan et al., J. Biol. Chem. 270(23),14047–14055 [1995]), is consistent with the supposition that the type Clectins are, in general, involved with the rapid recognition ofclustered carbohydrates. Together, these data suggest that type Clectins perform a number of critical physiological phenomena through therapid, relatively low affinity recognition of carbohydrates.

Given the obvious importance of the lectin proteins in numerousbiological processes, efforts are currently being made to identify novellectin proteins or proteins having sequence homology to lectin proteins.We herein describe the identification and characterization of novelpolypeptides having homology to a lectin protein, designated herein asPRO1270 polypeptides.

131. PRO1271

Efforts are being undertaken by both industry and academia to identifynew, native membrane-bound proteins. Many of these efforts are focusedon the screening of mammalian recombinant DNA libraries to identify thecoding sequences for novel transmembrane proteins. We herein describethe identification and characterization of novel transmembranepolypeptides, designated herein as PRO1271 polypeptides.

132. PRO1375

The proteins L1CAM, G6PD and P55 are each associated with various knowndisease states. Thus, the genomic loci of Fugu rubripes homologs of thehuman disease genes L1CAM, G6PD and P55 were analyzed. This analysis ledto the identification of putative protein 2 (PUT2), GENBANK locusAF026198, accession AF026198. (See GENBANK submission data). Thus, PUT2and proteins which have sequence identity with PUT2, are of interest.

133. PRO1385

Efforts are being undertaken by both industry and academia to identifynew, native secreted proteins. Many of these efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel secreted proteins. We herein describe theidentification and characterization of novel secreted polypeptides,designated herein as PRO1385 polypeptides.

134. PRO1387

Membrane-bound proteins of myelin are of interest because of theirpossible implications in various nervous system disorders associatedwith improper myelination. Myelin is a cellular sheath, formed by glialcells, that surrounds axons and axonal processes that enhances variouselectrochemical properties and provides trophic support to the neuron.Myelin is formed by Schwann cells in the peripheral nervous system (PNS)and by oligodendrocytes in the central nervous system (CNS). Impropermyelination of central and peripheral neurons occurs in a number ofpathologies and leads to improper signal conduction within the nervoussystems. Among the various demyelinating diseases Multiple Sclerosis isthe most notable.

The predominant integral membrane protein of the CNS myelin ofamphibians, reptiles, birds and mammals are proteolipid protein (PLP)and P0, the main glycoprotein in PNS myelin. (Schlieess and Stoffel,Biol. Chem. Hoppe Seyler (1991) 372(9):865–874). In view of theimportance of membrane-bound proteins of the myelin, efforts are beingundertaken by both industry and academia to identify and characterizevarious myelin proteins (see Stratmann and Jeserich, J. Neurochem (1995)64(6):2427–2436).

We herein describe the identification and characterization of novelpolypeptides having homology to myelin protein, designated herein asPRO1387 polypeptides.

135. PRO1384

One class of receptor proteins that has been of interest is the NKG2family of type II transmembrane molecules that are expressed in naturalkiller cells. These proteins, which have been shown to be covalentlyassociated with CD94, are involved in natural killer cell-mediatedrecognition of different HLA-allotypes (Plougastel, B. et al., Eur. J.Immunol. (1997) 27(11):2835–2839), and interact with majorhistocompatibility complex (MHC) class I to either inhibit or activatefunctional activity (Ho, EL. et al., Proc. Natl. Acad. Sci. (1998)95(11):6320–6325). Accordingly, the identification and characterizationof new members of this family of receptor proteins is of interest (seeHouchins JP, et al. J. Exp. Med. (1991) 173(4):1017–1020).

SUMMARY OF THE INVENTION

1. PRO281

A cDNA clone (DNA16422-1209) has been identified, having homology tonucleic acid encoding testis enhanced gene transcript (TEGT) proteinthat encodes a novel polypeptide, designated in the present applicationas “PRO281”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO281 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO281 polypeptide having the sequence of amino acid residuesfrom about 1 or about 15 to about 345, inclusive of FIG. 2 (SEQ IDNO:2), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO281 polypeptide comprising DNA hybridizing to thecomplement of the nucleic acid between about nucleotides 80 or about 122and about 1114, inclusive, of FIG. 1 (SEQ ID NO:1). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 209929(DNA 16422-1209) or (b) the complement of the nucleic acid molecule of(a). In a preferred embodiment, the nucleic acid comprises a DNAencoding the same mature polypeptide encoded by the human protein cDNAin ATCC Deposit No. 209929 (DNA16422-1209).

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 15 to about 345, inclusive of FIG. 2 (SEQ IDNO:2), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least 10 nucleotides and produced by hybridizing atest DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO281 polypeptide having the sequence of amino acid residuesfrom 1 or about 15 to about 345, inclusive of FIG. 2 (SEQ ID NO:2), or(b) the complement of the DNA molecule of (a), and, if the DNA moleculehas at least about an 80% sequence identity, preferably at least aboutan 85% sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO281 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, and itssoluble, i.e., transmembrane domain deleted or inactivated variants, oris complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from about aminoacid position 1 to about amino acid position 14 in the sequence of FIG.2 (SEQ ID NO:2). The multiple transmembrane domains have beententatively identified as extending from about amino acid position 83 toabout amino acid position 105, from about amino acid position 126 toabout amino acid position 146, from about amino acid position 158 toabout amino acid position 177, from about amino acid position 197 toabout amino acid position 216, from about amino acid position 218 toabout amino acid position 238, from about amino acid position 245 toabout amino acid position 265, and from about amino acid position 271 toabout amino acid position 290 in the PRO281 amino acid sequence (FIG. 2,SEQ ID NO:2).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 15 to about 345, inclusive of FIG. 2 (SEQ ID NO:2), or (b) thecomplement of the DNA of (a).

Another embodiment is directed to fragments of a PRO281 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 1 (SEQ ID NO:1).

In another embodiment, the invention provides isolated PRO281polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO281 polypeptide, which in certain embodiments, includes an amino acidsequence comprising residues 1 or about 15 to about 345 of FIG. 2 (SEQID NO:2).

In another aspect, the invention concerns an isolated PRO281polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 15 to about 345, inclusive of FIG. 2 (SEQ ID NO:2).

In a further aspect, the invention concerns an isolated PRO281polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 15 to about 345, inclusive of FIG. 2 (SEQ ID NO:2).

In yet another aspect, the invention concerns an isolated PRO281polypeptide, comprising the sequence of amino acid residues 1 or about15 to about 345, inclusive of FIG. 2 (SEQ ID NO:2), or a fragmentthereof sufficient to provide a binding site for an anti-PRO281antibody. Preferably, the PRO281 fragment retains a qualitativebiological activity of a native PRO281 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO281 polypeptide having the sequence ofamino acid residues from about 1 or about 15 to about 345, inclusive ofFIG. 2 (SEQ ID NO:2), or (b) the complement of the DNA molecule of (a),and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of a native PRO281 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO281 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO281 polypeptide by contacting thenative PRO281 polypeptide with a candidate molecule and monitoring abiological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO281 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

2. PRO276

A cDNA clone (DNA16435-1208) has been identified that encodes a novelpolypeptide having two transmembrane domains and designated in thepresent application as “PRO276.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO276 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO276 polypeptide having the sequence of amino acid residuesfrom about 1 to about 251, inclusive of FIG. 4 (SEQ ID NO:6), or (b) thecomplement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO276 polypeptide comprising DNA hybridizing to thecomplement of the nucleic acid between about residues 180 and about 932,inclusive, of FIG. 3 (SEQ ID NO:5). Preferably, hybridization occursunder stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 209930(DNA16435-1208), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.209930 (DNA16435-1208).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 1 to about 251, inclusive of FIG. 4 (SEQ IDNO:6), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least about 50 nucleotides, and preferably at leastabout 100 nucleotides and produced by hybridizing a test DNA moleculeunder stringent conditions with (a) a DNA molecule encoding a PRO276polypeptide having the sequence of amino acid residues from about 1 toabout 251, inclusive of FIG. 4 (SEQ ID NO:6), or (b) the complement ofthe DNA molecule of (a), and, if the DNA molecule has at least about an80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO276 polypeptide in its soluble,i.e. transmembrane domains deleted or inactivated variants, or iscomplementary to such encoding nucleic acid molecule. The transmembranedomains are at about amino acds 98–116 and 152–172.

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1to about 251, inclusive of FIG. 4 (SEQ ID NO:6), or (b) the complementof the DNA of (a).

Another embodiment is directed to fragments of a PRO276 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO276polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO276 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 through 251 of FIG. 4 (SEQ ID NO:6).

In another aspect, the invention concerns an isolated PRO276polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 to about 251, inclusive of FIG. 4 (SEQ ID NO:6).

In a further aspect, the invention concerns an isolated PRO276polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1through 251 of FIG. 4 (SEQ ID NO:6).

In yet another aspect, the invention concerns an isolated PRO276polypeptide, comprising the sequence of amino acid residues 1 to about251, inclusive of FIG. 4 (SEQ ID NO:6), or a fragment thereof sufficientto provide a binding site for an anti-PRO276 antibody. Preferably, thePRO276 fragment retains a qualitative biological activity of a nativePRO276 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO276 polypeptide having the sequence ofamino acid residues from about 1 to about 251, inclusive of FIG. 4 (SEQID NO:6), or (b) the complement of the DNA molecule of (a), and if thetest DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of a native PRO276 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO276 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO276 polypeptide, by contactingthe native PRO276 polypeptide with a candidate molecule and monitoring abiological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO276 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

3. PRO189

A cDNA clone (DNA21624-1391) has been identified that encodes a novelpolypeptide, designated in the present application as “PRO189”. PRO189polypeptides have a cytosolic fatty-acid binding domain.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO189 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO189 polypeptide having the sequence of amino acid residuesfrom about 1 to about 367, inclusive of FIG. 6 (SEQ ID NO:8), or (b) thecomplement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO189 polypeptide comprising DNA hybridizing to thecomplement of the nucleic acid between about residues 200 and about1300, inclusive, of FIG. 5 (SEQ ID NO:7). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 209917(DNA21624-1391), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.209917 (DNA21624-1391).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 1 to about 367, inclusive of FIG. 6 (SEQ IDNO:8), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule produced by hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO189 polypeptide havingthe sequence of amino acid residues from about 1 to about 367, inclusiveof FIG. 6 (SEQ ID NO:8), or (b) the complement of the DNA molecule of(a), and, if the DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), isolating the testDNA molecule.

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1to about 367, inclusive of FIG. 6 (SEQ ID NO:8), or (b) the complementof the DNA of (a).

In another embodiment, the invention provides isolated PRO189polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO189 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 through 367 of FIG. 6 (SEQ ID NO:8).

In another aspect, the invention concerns an isolated PRO189polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 to about 367, inclusive of FIG. 6 (SEQ ID NO:8).

In a further aspect, the invention concerns an isolated PRO189polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1through 367 of FIG. 6 (SEQ ID NO:8).

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO189 polypeptide having the sequence ofamino acid residues from about 1 to about 367, inclusive of FIG. 6 (SEQID NO:8), or (b) the complement of the DNA molecule of (a), and if thetest DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO189 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO189 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO189 polypeptide, by contactingthe native PRO189 polypeptide with a candidate molecule and monitoring abiological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO189 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

4. PRO190

Applicants have identified a cDNA clone that encodes a novel polypeptidehaving seven transmembrane domains and having sequence identity withCMP-sialic acid and UDP-galactose transporters, wherein the polypeptideis designated in the present application as “PRO190”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO190 polypeptide. In one aspect,the isolated nucleic acid comprises DNA encoding the PRO190 polypeptidehaving amino acid residues 1 through 424 of FIG. 9 (SEQ ID NO:14), or iscomplementary to such encoding nucleic acid sequence, and remains stablybound to it under at least moderate, and optionally, under highstringency conditions. The isolated nucleic acid sequence may comprisethe cDNA insert of the vector deposited on Jun. 2, 1998 with the ATCC asDNA23334-1392 which includes the nucleotide sequence encoding PRO190.

In another embodiment, the invention provides isolated PRO190polypeptide. In particular, the invention provides isolated nativesequence PRO190 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 through 424 of FIG. 9 (SEQ IDNO:14). An additional embodiment of the present invention is directed toan isolated PRO190 polypeptide, excluding the transmembrane domains.Optionally, the PRO190 polypeptide is obtained or is obtainable byexpressing the polypeptide encoded by the cDNA insert of the vectordeposited on Jun. 2, 1998 with the ATCC as DNA23334-1392.

In another embodiment, the invention provides an expressed sequence tag(EST) comprising the nucleotide sequence of SEQ ID NO:15.

5. PRO341

A cDNA clone (DNA26288-1239) has been identified that encodes a noveltransmembrane polypeptide, designated in the present application as“PRO341”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO341 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO341 polypeptide having the sequence of amino acid residuesfrom about 1 or about 18 to about 458, inclusive of FIG. 12 (SEQ IDNO:20), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO341 polypeptide comprising DNA hybridizing to thecomplement of the nucleic acid between about nucleotides 380 or about431 and about 1753, inclusive, of FIG. 11 (SEQ ID NO:19). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 209792(DNA26288-1239) or (b) the complement of the nucleic acid molecule of(a). In a preferred embodiment, the nucleic acid comprises a DNAencoding the same mature polypeptide encoded by the human protein cDNAin ATCC Deposit No. 209792 (DNA26288-1239).

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 18 to about 458, inclusive of FIG. 12 (SEQ IDNO:20), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least 165 nucleotides and produced by hybridizing atest DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO341 polypeptide having the sequence of amino acid residuesfrom 1 or about 18 to about 458, inclusive of FIG. 12 (SEQ ID NO:20), or(b) the complement of the DNA molecule of (a), and, if the DNA moleculehas at least about an 80% sequence identity, preferably at least aboutan 85% sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO341 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, and itssoluble, i.e., transmembrane domain deleted or inactivated variants, oris complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from about aminoacid position 1 to about amino acid position 17 in the sequence of FIG.12 (SEQ ID NO:20). The transmembrane domains have been tentativelyidentified as extending from about amino acid position 171 to aboutamino acid position 190, from about amino acid position 220 to aboutamino acid position 239, from about amino acid position 259 to aboutamino acid position 275, from about amino acid position 286 to aboutamino acid position 305, from about amino acid position 316 to aboutamino acid position 335, from about amino acid position 353 to aboutamino acid position 378 and from about amino acid position 396 to aboutamino acid position 417 in the PRO341 amino acid sequence (FIG. 12, SEQID NO:20).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 18 to about 458, inclusive of FIG. 12 (SEQ ID NO:20), or (b)the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO341 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 11 (SEQ ID NO:19).

In another embodiment, the invention provides isolated PRO341polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO341 polypeptide, which in certain embodiments, includes an amino acidsequence comprising residues 1 or about 18 to about 458 of FIG. 12 (SEQID NO:20).

In another aspect, the invention concerns an isolated PRO341polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 18 to about 458, inclusive of FIG. 12 (SEQ ID NO:20).

In a further aspect, the invention concerns an isolated PRO341polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 18 to about 458, inclusive of FIG. 12 (SEQ ID NO:20).

In yet another aspect, the invention concerns an isolated PRO341polypeptide, comprising the sequence of amino acid residues 1 or about18 to about 458, inclusive of FIG. 12 (SEQ ID NO:20), or a fragmentthereof sufficient to provide a binding site for an anti-PRO341antibody. Preferably, the PRO341 fragment retains a qualitativebiological activity of a native PRO341 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO341 polypeptide having the sequence ofamino acid residues from about 1 or about 18 to about 458, inclusive ofFIG. 12 (SEQ ID NO:20), or (b) the complement of the DNA molecule of(a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In another embodiment, the invention provides an expressed sequence tag(EST) designated herein as DNA12920 comprising the nucleotide sequenceof SEQ ID NO:21 (see FIG. 13).

6. PRO180

A cDNA clone (DNA26843-1389) has been identified that encodes a novelpolypeptide having multiple transmembrane domains designated in thepresent application as “PRO180”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO180 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO180 polypeptide having the sequence of amino acid residuesfrom about 1 to about 266, inclusive of FIG. 15 (SEQ ID NO:23), or (b)the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO180 polypeptide comprising DNA hybridizing to thecomplement of the nucleic acid between about nucleotides 121 and about918, inclusive, of FIG. 14 (SEQ ID NO:22). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203099(DNA26843-1389), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203099 (DNA26843-1389).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 1 to about 266, inclusive of FIG. 15 (SEQ IDNO:23), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least about 50 nucleotides, and preferably at leastabout 100 nucleotides and produced by hybridizing a test DNA moleculeunder stringent conditions with (a) a DNA molecule encoding a PRO180polypeptide having the sequence of amino acid residues from about 1 toabout 266, inclusive of FIG. 15 (SEQ ID NO:23), or (b) the complement ofthe DNA molecule of (a), and, if the DNA molecule has at least about an80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO180 polypeptide in its solubleform, i.e. transmembrane domains deleted or inactivated variants, or iscomplementary to such encoding nucleic acid molecule. The transmembranedomains are shown in FIG. 15. It is believed that PRO180 has a type IItransmembrane domain from about amino acids 13–33 of SEQ ID NO:23.

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1to about 266, inclusive of FIG. 15 (SEQ ID NO:23), or (b) the complementof the DNA of (a).

Another embodiment is directed to fragments of a PRO180 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO180polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO180 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 through 266 of FIG. 15 (SEQ ID NO:23).

In another aspect, the invention concerns an isolated PRO180polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 to about 266, inclusive of FIG. 15 (SEQ ID NO:23).

In a further aspect, the invention concerns an isolated PRO180polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1through 266 of FIG. 15 (SEQ ID NO:23).

In yet another aspect, the invention concerns an isolated PRO180polypeptide, comprising the sequence of amino acid residues 1 to about266, inclusive of FIG. 15 (SEQ ID NO :23), or a fragment thereofsufficient to provide a binding site for an anti-PRO180 antibody.Preferably, the PRO180 fragment retains a qualitative biologicalactivity of a native PRO180 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO180 polypeptide having the sequence ofamino acid residues from about 1 to about 266, inclusive of FIG. 15 (SEQID NO:23), or (b) the complement of the DNA molecule of (a), and if thetest DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO180 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO180 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO180 polypeptide, by contactingthe native PRO180 polypeptide with a candidate molecule and monitoring abiological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO180 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

In another embodiment, the invention provides an expressed sequence tag(EST) (DNA12922) comprising the nucleotide sequence of FIG. 16 (SEQ IDNO:24).

7. PRO194

Applicants have identified a cDNA clone that encodes a noveltransmembrane polypeptide, wherein the polypeptide is designated in thepresent application as “PRO194”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO194 polypeptide. In one aspect,the isolated nucleic acid comprises DNA encoding the PRO194 polypeptidehaving amino acid residues 1 to 264 of FIG. 18 (SEQ ID NO:28), or iscomplementary to such encoding nucleic acid sequence, and remains stablybound to it under at least moderate, and optionally, under highstringency conditions. In other aspects, the isolated nucleic acidcomprises DNA encoding the PRO194 polypeptide having amino acid residuesabout 18 to 264 of FIG. 18 (SEQ ID NO:28) or amino acid 1 or about 18 toX of FIG. 18 (SEQ ID NO:28), where X is any amino acid from 96 to 105 ofFIG. 18 (SEQ ID NO:28), or is complementary to such encoding nucleicacid sequence, and remains stably bound to it under at least moderate,and optionally, under high stringency conditions. The isolated nucleicacid sequence may comprise the cDNA insert of the DNA26844-1394 vectordeposited on Jun. 2, 1998 as ATCC 209926 which includes the nucleotidesequence encoding PRO194.

In another embodiment, the invention provides isolated PRO194polypeptide. In particular, the invention provides isolated nativesequence PRO194polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 to 264 of FIG. 18 (SEQ ID NO:28).Additional embodiments of the present invention are directed to PRO194polypeptides comprising amino acids about 18 to 264 of FIG. 18 (SEQ IDNO:28) or amino acid 1 or about 18 to X of FIG. 18 (SEQ ID NO:28), whereX is any amino acid from 96 to 105 of FIG. 18 (SEQ ID NO:28).Optionally, the PRO194 polypeptide is obtained or is obtainable byexpressing the polypeptide encoded by the cDNA insert of theDNA26844-1394 vector deposited on Jun. 2, 1998 as ATCC 209926.

8. PRO203

Applicants have identified a cDNA clone that encodes a novel polypeptidehaving sequence identity to glutathione-S-transferase, wherein thepolypeptide is designated in the present application as “PRO203”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO203 polypeptide. In one aspect,the isolated nucleic acid comprises DNA encoding the PRO203 polypeptidehaving amino acid residues 1 to 347 of FIG. 20 (SEQ ID NO:30), or iscomplementary to such encoding nucleic acid sequence, and remains stablybound to it under at least moderate, and optionally, under highstringency conditions. In other aspects, the isolated nucleic acidcomprises DNA encoding the PRO203 polypeptide having amino acid residuesX to 347 of FIG. 20 (SEQ ID NO:30), where X is any amino acid from 83 to92 of FIG. 20 (SEQ ID NO:30), or is complementary to such encodingnucleic acid sequence, and remains stably bound to it under at leastmoderate, and optionally, under high stringency conditions. The isolatednucleic acid sequence may comprise the cDNA insert of the DNA30862-1396vector deposited on Jun. 2, 1998, as ATCC 209920 which includes thenucleotide sequence encoding PRO203.

In another embodiment, the invention provides isolated PRO203polypeptide. In particular, the invention provides isolated nativesequence PRO203 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 to 347 of FIG. 20 (SEQ ID NO:30).Additional embodiments of the present invention are directed to PRO203polypeptides comprising amino acid X to 347 of FIG. 20 (SEQ ID NO:30),where X is any amino acid from 83 to 92 of FIG. 20 (SEQ ID NO:30).Optionally, the PRO203 polypeptide is obtained or is obtainable byexpressing the polypeptide encoded by the cDNA insert of theDNA30862-1396 vector deposited on Jun. 2, 1998, as ATCC 209920.

In another embodiment, the invention provides an expressed sequence tag(EST) designated herein as DNA15618 which comprises the nucleotidesequence of FIG. 21 (SEQ ID NO:31).

9. PRO290

A cDNA clone (DNA35680-1212) has been identified which encodes apolypeptide designated in the present application as “PRO290.” PRO290polypeptides have sequence identity with NTII-1, FAN and beige.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO290 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO290 polypeptide having the sequence of amino acid residuesfrom about 1 to about 1003, inclusive of FIG. 23 (SEQ ID NO:33), or (b)the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO290 polypeptide comprising DNA hybridizing to thecomplement of the nucleic acid between about residues 293 and about3301, inclusive, of FIG. 22 (SEQ ID NO:32). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 209790(DNA35680-1212), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.209790 (DNA35680-1212).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 1 to about 1003, inclusive of FIG. 23 (SEQ IDNO:33), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule produced by hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO290 polypeptide havingthe sequence of amino acid residues from about 1 to about 1003,inclusive of FIG. 23 (SEQ ID NO:33), or (b) the complement of the DNAmolecule of (a), and, if the DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), isolating the testDNA molecule.

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1to about 1003, inclusive of FIG. 23 (SEQ ID NO:33), or (b) thecomplement of the DNA of (a).

In another embodiment, the invention provides isolated PRO290polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO290 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 through 1003 of FIG. 23 (SEQ ID NO:33).

In another aspect, the invention concerns an isolated PRO290polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 to about 1003, inclusive of FIG. 23 (SEQ ID NO:33).

In a further aspect, the invention concerns an isolated PRO290polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1through 1003 of FIG. 23 (SEQ ID NO:33).

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO290 polypeptide having the sequence ofamino acid residues from about 1 to about 1003, inclusive of FIG. 23(SEQ ID NO:33), or (b) the complement of the DNA molecule of (a), and ifthe test DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO290 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO290 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO290 polypeptide, by contactingthe native PRO290 polypeptide with a candidate molecule and monitoring abiological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO290 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

10. PRO874

Applicants have identified a cDNA clone that encodes a novel multi-spantransmembrane polypeptide, which is designated in the presentapplication as “PRO874”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO874 polypeptide. In one aspect,the isolated nucleic acid comprises DNA encoding the PRO874 polypeptidehaving amino acid residues 1 to 321 of FIG. 25 (SEQ ID NO:36), or iscomplementary to such encoding nucleic acid sequence, and remains stablybound to it under at least moderate, and optionally, under highstringency conditions. In other aspects, the isolated nucleic acidcomprises DNA encoding the PRO874 polypeptide having amino acid fromabout X to 321 of FIG. 25 (SEQ ID NO:36), where X is any amino acid fromabout 270 to about 279 of FIG. 25 (SEQ ID NO:36), or is complementary tosuch encoding nucleic acid sequence, and remains stably bound to itunder at least moderate, and optionally, under high stringencyconditions. The isolated nucleic acid sequence may comprise the cDNAinsert of the DNA40621-1440 vector deposited on Jun. 2, 1998, as ATCC209922 which includes the nucleotide sequence encoding PRO874.

In another embodiment, the invention provides isolated PRO874polypeptide. In particular, the invention provides isolated nativesequence PRO874 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 to 321 of FIG. 25 (SEQ ID NO:36).Additional embodiments of the present invention are directed to PRO874polypeptides comprising amino acids X to 321 of FIG. 25 (SEQ ID NO:36),where X is any amino acid from about 270 to about 279 of FIG. 25 (SEQ IDNO:36). Optionally, the PRO874 polypeptide is obtained or is obtainableby expressing the polypeptide encoded by the cDNA insert of theDNA40621-1440 vector deposited on Jun. 2, 1998, as ATCC 209922.

11. PRO710

Applicants have identified a cDNA clone that encodes a novel polypeptidehaving homology to CDC45 protein, wherein the polypeptide is designatedin the present application as “PRO710”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO710 polypeptide. In one aspect,the isolated nucleic acid comprises DNA encoding the PRO710 polypeptidehaving amino acid residues 1 to 566 of FIG. 27 (SEQ ID NO:41), or iscomplementary to such encoding nucleic acid sequence, and remains stablybound to it under at least moderate, and optionally, under highstringency conditions. In other aspects, the isolated nucleic acidcomprises DNA encoding the PRO710 polypeptide having amino acid residuesabout 33 to 566 of FIG. 27 (SEQ ID NO:41) or amino acid 1 or about 33 toX of FIG. 27 (SEQ ID NO:41), where X is any amino acid from 449 to 458of FIG. 27 (SEQ ID NO:41), or is complementary to such encoding nucleicacid sequence, and remains stably bound to it under at least moderate,and optionally, under high stringency conditions. The isolated nucleicacid sequence may comprise the cDNA insert of the DNA44161-1434 vectordeposited on May 27, 1998 as ATCC 209907 which includes the nucleotidesequence encoding PRO710.

In another embodiment, the invention provides isolated PRO710polypeptide. In particular, the invention provides isolated nativesequence PRO710polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 to 566 of FIG. 27 (SEQ ID NO:41).Additional embodiments of the present invention are directed to PRO710polypeptides comprising amino acids about 33 to 566 of FIG. 27 (SEQ IDNO:41) or amino acid 1 or about 33 to X of FIG. 27 (SEQ ID NO:41), whereX is any amino acid from 449 to 458 of FIG. 27 (SEQ ID NO:41).Optionally, the PRO710 polypeptide is obtained or is obtainable byexpressing the polypeptide encoded by the cDNA insert of theDNA44161-1434 vector deposited on May 27, 1998 as ATCC 209907.

In another embodiment, the invention provides an expressed sequence tag(EST) designated herein as DNA38190 comprising the nucleotide sequenceof FIG. 28 (SEQ ID NO:42).

12. PRO1151

A cDNA clone (DNA44694-1500) has been identified, having homology tonucleic acid encoding C1q protein, that encodes a novel polypeptide,designated in the present application as “PRO1151”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1151 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1151 polypeptide having the sequence of amino acidresidues from about 1 or about 21 to about 259, inclusive of FIG. 30(SEQ ID NO:47), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1151 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about nucleotides 272 orabout 332 and about 1048, inclusive, of FIG. 29 (SEQ ID NO:46).Preferably, hybridization occurs under stringent hybridization and washconditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203114(DNA44694-1500) or (b) the complement of the nucleic acid molecule of(a). In a preferred embodiment, the nucleic acid comprises a DNAencoding the same mature polypeptide encoded by the human protein cDNAin ATCC Deposit No. 203114 (DNA44694-1500).

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 21 to about 259, inclusive of FIG. 30 (SEQ IDNO:47), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least 10 nucleotides and produced by hybridizing atest DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1151 polypeptide having the sequence of amino acidresidues from 1 or about 21 to about 259, inclusive of FIG. 30 (SEQ IDNO:47), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, preferably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1151 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, or iscomplementary to such encoding nucleic acid molecule. The signal peptidehas been tentatively identified as extending from about amino acidposition 1 to about amino acid position 20 in the sequence of FIG. 30(SEQ ID NO:47).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 21 to about 259, inclusive of FIG. 30 (SEQ ID NO:47), or (b)the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1151 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 29 (SEQ ID NO:46).

In another embodiment, the invention provides isolated PRO1151polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO1151 polypeptide, which in certain embodiments, includes an aminoacid sequence comprising residues 1 or about 21 to about 259 of FIG. 30(SEQ ID NO:47).

In another aspect, the invention concerns an isolated PRO1151polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 21 to about 259, inclusive of FIG. 30 (SEQ ID NO:47).

In a further aspect, the invention concerns an isolated PRO1151polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 21 to about 259, inclusive of FIG. 30 (SEQ ID NO:47).

In yet another aspect, the invention concerns an isolated PRO1151polypeptide, comprising the sequence of amino acid residues 1 or about21 to about 259, inclusive of FIG. 30 (SEQ ID NO:47), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1151antibody. Preferably, the PRO1151 fragment retains a qualitativebiological activity of a native PRO1151 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1151 polypeptide having the sequence ofamino acid residues from about 1 or about 21 to about 259, inclusive ofFIG. 30 (SEQ ID NO:47), or (b) the complement of the DNA molecule of(a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1151 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1151 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1151 polypeptide by contactingthe native PRO1151 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1151 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

13. PRO1282

A cDNA clone (DNA45495-1550) has been identified that encodes a novelpolypeptide having sequence identity with leucine rich repeat proteinsand designated in the present application as “PRO1282.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1282 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1282 polypeptide having the sequence of amino acidresidues from about 24 to about 673, inclusive of FIG. 32 (SEQ IDNO:52), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1282 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 189 and about2138, inclusive, of FIG. 31 (SEQ ID NO:51). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203156(DNA45495-1550), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203156 (DNA45495-1550).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 24 to about 673, inclusive of FIG. 32 (SEQ IDNO:52), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least about 50 nucleotides, and preferably at leastabout 100 nucleotides and produced by hybridizing a test DNA moleculeunder stringent conditions with (a) a DNA molecule encoding a PRO1282polypeptide having the sequence of amino acid residues from about 24 toabout 673, inclusive of FIG. 32 (SEQ ID NO:52), or (b) the complement ofthe DNA molecule of (a), and, if the DNA molecule has at least about an80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1282 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, and itssoluble, i.e. transmembrane domain deleted or inactivated variants, oris complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from amino acidposition 1 through about amino acid position 23 in the sequence of FIG.32 (SEQ ID NO:52). The transmembrane domain has been tentativelyidentified as extending from about amino acid position 579 through aboutamino acid position 599 in the PRO1282 amino acid sequence (FIG. 32, SEQID NO:52).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 24to about 673, inclusive of FIG. 32 (SEQ ID NO:52), or (b) the complementof the DNA of (a).

Another embodiment is directed to fragments of a PRO1282 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1282polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1282 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 24 through 673 of FIG. 32 (SEQ ID NO:52).

In another aspect, the invention concerns an isolated PRO1282polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues24 to about 673, inclusive of FIG. 32 (SEQ ID NO:52).

In a further aspect, the invention concerns an isolated PRO1282polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 24through 673 of FIG. 32 (SEQ ID NO:52).

In yet another aspect, the invention concerns an isolated PRO1282polypeptide, comprising the sequence of amino acid residues 24 to about673, inclusive of FIG. 32 (SEQ ID NO:52), or a fragment thereofsufficient to provide a binding site for an anti-PRO1282 antibody.Preferably, the PRO1282 fragment retains a qualitative biologicalactivity of a native PRO1282 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1282 polypeptide having the sequence ofamino acid residues from about 24 to about 673, inclusive of FIG. 32(SEQ ID NO:52), or (b) the complement of the DNA molecule of (a), and ifthe test DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1282 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1282 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1282 polypeptide, by contactingthe native PRO1282 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1282 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

14. PRO358

Applicants have identified a novel cDNA clone that encodes novel humanToll polypeptides, designated in the present application as PRO358.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising a DNA encoding a polypeptide having at least about80% sequence identity, preferably at least about 85% sequence identity,more preferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding aPRO358 polypeptide having amino acids 20 to 575 of FIG. 34 (SEQ IDNO:57), or (b) the complement of the DNA molecule of (a). Thecomplementary DNA molecule preferably remains stably bound to suchencoding nucleic acid sequence under at least moderate, and optionally,under high stringency conditions.

In a further embodiment, the isolated nucleic acid molecule comprises apolynucleotide that has at least about 90%, preferably at least about95% sequence identity with a polynucleotide encoding a polypeptidecomprising the sequence of amino acids 1 to 811 of FIG. 34 (SEQ IDNO:57).

In a specific embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding native or variant PRO358polypeptide, with or without the N-terminal signal sequence, and with orwithout the transmembrane regions of the respective full-lengthsequences. In one aspect, the isolated nucleic acid comprises DNAencoding a mature, full-length native PRO358 polypeptide having aminoacid residues 1 to 811 of FIG. 34 (SEQ ID NO:57), or is complementary tosuch encoding nucleic acid sequence. In another aspect, the inventionconcerns an isolated nucleic acid molecule that comprises DNA encoding anative PRO358 polypeptide without an N-terminal signal sequence, or iscomplementary to such encoding nucleic acid sequence. In yet anotherembodiment, the invention concerns nucleic acid encodingtransmembrane-domain deleted or inactivated forms of the full-lengthnative PRO358 protein.

In another embodiment, the invention provides an isolated nucleic acidmolecule which comprises the clone (DNA 47361-1249) deposited on Nov. 7,1997, under ATCC number 209431.

In a specific embodiment, the invention provides a vector comprising apolynucleotide having at least about 80% sequence identity, preferablyat least about 85% sequence identity, more preferably at least about 90%sequence identity, most preferably at least about 95% sequence identitywith a polynucleotide encoding a polypeptide comprising the sequence ofamino acids 20 to 811 of FIG. 34 (SEQ ID NO:57), or the complement ofsuch polynucleotide. In a particular embodiment, the vector comprisesDNA encoding the novel Toll homologue (PRO358), with or without theN-terminal signal sequence (about amino acids 1 to 19), or atransmembrane-domain (about amino acids 576–595) deleted or inactivatedvariant thereof, or the extracellular domain (about amino acids 20 to595) of the mature protein, or a protein comprising any one of thesesequences. A host cell comprising such a vector is also provided.

In another embodiment, the invention provides isolated PRO358polypeptides. The invention further provides an isolated native sequencePRO358 polypeptide, or variants thereof. In particular, the inventionprovides an isolated native sequence PRO358 polypeptide, which incertain embodiments, includes the amino acid sequence comprisingresidues 20 to 575, or 20 to 811, or 1 to 811 of FIG. 34 (SEQ ID NO:57).

In yet another embodiment, the invention concerns agonists andantagonists of the native PRO358 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO358 antibody.

In a further embodiment, the invention concerns screening assays toidentify agonists or antagonists of the native PRO358 polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO358 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

The invention further concerns a composition comprising an antibodyspecifically binding a PRO358 polypeptide, in combination with apharmaceutically acceptable carrier.

The invention also concerns a method of treating septic shock comprisingadministering to a patient an effective amount of an antagonist of aPRO358 polypeptide. In a specific embodiment, the antagonist is ablocking antibody specifically binding a native PRO358 polypeptide.

15. PRO1310

A cDNA clone (DNA47394-1572) has been identified that encodes a novelpolypeptide having sequence identity with carboxypeptidase X2 anddesignated in the present application as “PRO1310.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1310 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1310 polypeptide having the sequence of amino acidresidues from about 26 to about 765, inclusive of FIG. 36 (SEQ IDNO:62), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1310 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 401 and about2593, inclusive, of FIG. 35 (SEQ ID NO:61). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203109(DNA47394-1572), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203109 (DNA47394-1572).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 26 to about 765, inclusive of FIG. 36 (SEQ IDNO:62), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least about 50 nucleotides, and preferably at leastabout 100 nucleotides and produced by hybridizing a test DNA moleculeunder stringent conditions with (a) a DNA molecule encoding a PRO1310polypeptide having the sequence of amino acid residues from about 26 toabout 765, inclusive of FIG. 36 (SEQ ID NO:62), or (b) the complement ofthe DNA molecule of (a), and, if the DNA molecule has at least about an80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 26to about 765, inclusive of FIG. 36 (SEQ ID NO:62), or (b) the complementof the DNA of (a).

In another embodiment, the invention provides isolated PRO1310polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1310 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 26 through 765 of FIG. 36 (SEQ ID NO:62).

In another aspect, the invention concerns an isolated PRO1310polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues26 to about 765, inclusive of FIG. 36 (SEQ ID NO:62).

In a further aspect, the invention concerns an isolated PRO1310polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 26through 765 of FIG. 36 (SEQ ID NO:62).

In yet another aspect, the invention concerns an isolated PRO1310polypeptide, comprising the sequence of amino acid residues 26 to about765, inclusive of FIG. 36 (SEQ ID NO:62), or a fragment thereofsufficient to provide a binding site for an anti-PRO1310 antibody.Preferably, the PRO1310 fragment retains a qualitative biologicalactivity of a native PRO1310 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1310 polypeptide having the sequence ofamino acid residues from about 26 to about 765, inclusive of FIG. 36(SEQ ID NO:62), or (b) the complement of the DNA molecule of (a), and ifthe test DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1310 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1310 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1310 polypeptide, by contactingthe native PRO1310 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1310 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

16. PRO698

Applicants have identified a cDNA clone that encodes a novel polypeptidehaving homology to olfactomedin, wherein the polypeptide is designatedin the present application as “PRO698”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO698 polypeptide. In one aspect,the isolated nucleic acid comprises DNA encoding the PRO698 polypeptidehaving amino acid residues 1 to 510 of FIG. 38 (SEQ ID NO:67), or iscomplementary to such encoding nucleic acid sequence, and remains stablybound to it under at least moderate, and optionally, under highstringency conditions. In other aspects, the isolated nucleic acidcomprises DNA encoding the PRO698 polypeptide having amino acid residuesabout 21 to 510 of FIG. 38 (SEQ ID NO:67), or is complementary to suchencoding nucleic acid sequence, and remains stably bound to it under atleast moderate, and optionally, under high stringency conditions. Theisolated nucleic acid sequence may comprise the cDNA insert of theDNA48320-1433 vector deposited on May 27, 1998 as ATCC 209904 whichincludes the nucleotide sequence encoding PRO698.

In another embodiment, the invention provides isolated PRO698polypeptide. In particular, the invention provides isolated nativesequence PRO698 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 to 510 of FIG. 38 (SEQ ID NO:67).Additional embodiments of the present invention are directed to PRO698polypeptides comprising amino acids about 21 to 510 of FIG. 38 (SEQ IDNO:67). Optionally, the PRO698 polypeptide is obtained or is obtainableby expressing the polypeptide encoded by the cDNA insert of theDNA48320-1433 vector deposited on May 27, 1998 as ATCC 209904.

In another embodiment, the invention provides an expressed sequence tag(EST) designated herein as DNA39906 comprising the nucleotide sequenceof FIG. 39 (SEQ ID NO:68).

17. PRO732

Applicants have identified a cDNA clone that encodes a novel polypeptidehaving homology to the human placental protein Diff33, wherein thepolypeptide is designated in the present application as “PRO732”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO732 polypeptide. In one aspect,the isolated nucleic acid comprises DNA encoding the PRO732 polypeptidehaving amino acid residues 1 to 453 of FIG. 41 (SEQ ID NO:73), or iscomplementary to such encoding nucleic acid sequence, and remains stablybound to it under at least moderate, and optionally, under highstringency conditions. In other aspects, the isolated nucleic acidcomprises DNA encoding the PRO732 polypeptide having amino acid residuesabout 29 to 453 of FIG. 41 (SEQ ID NO:73) or amino acid 1 or about 29 toX of FIG. 41 (SEQ ID NO:73), where X is any amino acid from 31 to 40 ofFIG. 41 (SEQ ID NO:73), or is complementary to such encoding nucleicacid sequence, and remains stably bound to it under at least moderate,and optionally, under high stringency conditions. The isolated nucleicacid sequence may comprise the cDNA insert of the DNA48334-1435 vectordeposited on Jun. 2, 1998 as ATCC 209924 which includes the nucleotidesequence encoding PRO732.

In another embodiment, the invention provides isolated PRO732polypeptide. In particular, the invention provides isolated nativesequence PRO732 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 to 453 of FIG. 41 (SEQ ID NO:73).Additional embodiments of the present invention are directed to PRO732polypeptides comprising amino acids about 29 to 453 of FIG. 41 (SEQ IDNO:73) or amino acid 1 or about 29 to X of FIG. 41 (SEQ ID NO:73), whereX is any amino acid from 31 to 40 of FIG. 41 (SEQ ID NO:73). Optionally,the PRO732 polypeptide is obtained or is obtainable by expressing thepolypeptide encoded by the cDNA insert of the DNA48334-1435 vectordeposited on Jun. 2, 1998 as ATCC 209924.

In another embodiment, the invention provides an expressed sequence tag(EST) designated herein as DNA20239 comprising the nucleotide sequenceof FIG. 42 (SEQ ID NO:74).

In another embodiment, the invention provides an expressed sequence tag(EST) designated herein as DNA38050 comprising the nucleotide sequenceof FIG. 43 (SEQ ID NO:75).

In another embodiment, the invention provides an expressed sequence tag(EST) designated herein as DNA40683 comprising the nucleotide sequenceof FIG. 44 (SEQ ID NO:76).

In another embodiment, the invention provides an expressed sequence tag(EST) designated herein as DNA42580 comprising the nucleotide sequenceof FIG. 45 (SEQ ID NO:77).

18. PRO1120

A cDNA clone (DNA48606-1479) has been identified that encodes a novelpolypeptide having homology sulfatases, designated in the presentapplication as “PRO1120.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1120 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1120 polypeptide having the sequence of amino acidresidues from about 18 to about 867, inclusive of FIG. 47 (SEQ IDNO:84), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1120 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 659 and about3208, inclusive, of FIG. 46 (SEQ ID NO:83). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203040(DNA48606-1479), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203040 (DNA48606-1479).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 18 to about 867, inclusive of FIG. 47 (SEQ IDNO:84), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least about 50 nucleotides and preferably at leastabout 100 nucleotides and produced by hybridizing a test DNA moleculeunder stringent conditions with (a) a DNA molecule encoding a PRO1120polypeptide having the sequence of amino acid residues from about 18 toabout 867, inclusive of FIG. 47 (SEQ ID NO:84), or (b) the complement ofthe DNA molecule of (a), and, if the DNA molecule has at least about an80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1120 polypeptide, with or withoutthe N-terminal signal sequence, or is complementary to such encodingnucleic acid molecule. The signal peptide has been tentativelyidentified as extending from amino acid position 1 through about aminoacid position 17 in the sequence of FIG. 47 (SEQ ID NO:84).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 18to about 867, inclusive of FIG. 47 (SEQ ID NO:84), or (b) the complementof the DNA of (a).

Another embodiment is directed to fragments of a PRO1120 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1120polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1120 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 18 to 867 of FIG. 47 (SEQ ID NO:84).

In another aspect, the invention concerns an isolated PRO1120polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues18 to about 867, inclusive of FIG. 47 (SEQ ID NO:84).

In a further aspect, the invention concerns an isolated PRO1120polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 18 to867 of FIG. 47 (SEQ ID NO:84).

In yet another aspect, the invention concerns an isolated PRO1120polypeptide, comprising the sequence of amino acid residues 18 to about867, inclusive of FIG. 47 (SEQ ID NO:84), or a fragment thereofsufficient to provide a binding site for an anti-PRO1120 antibody.Preferably, the PRO1120 fragment retains a qualitative biologicalactivity of a native PRO1120 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1120 polypeptide having the sequence ofamino acid residues from about 18 to about 867, inclusive of FIG. 47(SEQ ID NO:84), or (b) the complement of the DNA molecule of (a), and ifthe test DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1120 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1120 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1120 polypeptide, by contactingthe native PRO1120 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1120 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

19. PRO537

A cDNA clone (DNA49141-1431) has been identified that encodes a novelsecreted polypeptide, designated in the present application as “PRO537”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO537 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO537 polypeptide having the sequence of amino acid residuesfrom about 1 or about 32 to about 115, inclusive of FIG. 49 (SEQ IDNO:95), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO537 polypeptide comprising DNA hybridizing to thecomplement of the nucleic acid between about nucleotides 97 or about 190and about 441, inclusive, of FIG. 48 (SEQ ID NO:94). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203003(DNA49141-1431) or (b) the complement of the nucleic acid molecule of(a). In a preferred embodiment, the nucleic acid comprises a DNAencoding the same mature polypeptide encoded by the human protein cDNAin ATCC Deposit No. 203003 (DNA49141-1431).

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 32 to about 115, inclusive of FIG. 49 (SEQ IDNO:95), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least 10 nucleotides and produced by hybridizing atest DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO537 polypeptide having the sequence of amino acid residuesfrom 1 or about 32 to about 115, inclusive of FIG. 49 (SEQ ID NO:95), or(b) the complement of the DNA molecule of (a), and, if the DNA moleculehas at least about an 80% sequence identity, preferably at least aboutan 85% sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO537 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, or iscomplementary to such encoding nucleic acid molecule. The signal peptidehas been tentatively identified as extending from about amino acidposition 1 to about amino acid position 31 in the sequence of FIG. 49(SEQ ID NO:95).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 32 to about 115, inclusive of FIG. 49 (SEQ ID NO:95), or (b)the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO537 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 48 (SEQ ID NO:94).

In another embodiment, the invention provides isolated PRO537polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO537 polypeptide, which in certain embodiments, includes an amino acidsequence comprising residues 1 or about 32 to about 115 of FIG. 49 (SEQID NO:95).

In another aspect, the invention concerns an isolated PRO537polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 32 to about 115, inclusive of FIG. 49 (SEQ ID NO:95).

In a further aspect, the invention concerns an isolated PRO537polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 32 to about 115, inclusive of FIG. 49 (SEQ ID NO:95).

In yet another aspect, the invention concerns an isolated PRO537polypeptide, comprising the sequence of amino acid residues 1 or about32 to about 115, inclusive of FIG. 49 (SEQ ID NO:95), or a fragmentthereof sufficient to provide a binding site for an anti-PRO537antibody. Preferably, the PRO537 fragment retains a qualitativebiological activity of a native PRO537 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO537 polypeptide having the sequence ofamino acid residues from about 1 or about 32 to about 115, inclusive ofFIG. 49 (SEQ ID NO:95), or (b) the complement of the DNA molecule of(a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

20. PRO536

A cDNA clone (DNA49142-1430) has been identified, that encodes a novelsecreted polypeptide, designated in the present application as “PRO536”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO536 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO536 polypeptide having the sequence of amino acid residuesfrom about 1 or about 26 to about 313, inclusive of FIG. 51 (SEQ IDNO:97), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO536 polypeptide comprising DNA hybridizing to thecomplement of the nucleic acid between about nucleotides 48 or about 123and about 986, inclusive, of FIG. 50 (SEQ ID NO:96). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203002(DNA49142-1430) or (b) the complement of the nucleic acid molecule of(a). In a preferred embodiment, the nucleic acid comprises a DNAencoding the same mature polypeptide encoded by the human protein cDNAin ATCC Deposit No. 203002 (DNA49142-1430).

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 26 to about 313, inclusive of FIG. 51 (SEQ IDNO:97), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least 10 nucleotides and produced by hybridizing atest DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO536 polypeptide having the sequence of amino acid residuesfrom 1 or about 26 to about 313, inclusive of FIG. 51 (SEQ ID NO:97), or(b) the complement of the DNA molecule of (a), and, if the DNA moleculehas at least about an 80% sequence identity, preferably at least aboutan 85% sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO536 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, or iscomplementary to such encoding nucleic acid molecule. The signal peptidehas been tentatively identified as extending from about amino acidposition 1 to about amino acid position 25 in the sequence of FIG. 51(SEQ ID NO:97).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 26 to about 313, inclusive of FIG. 51 (SEQ ID NO:97), or (b)the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO536 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 50 (SEQ ID NO:96).

In another embodiment, the invention provides isolated PRO536polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO536 polypeptide, which in certain embodiments, includes an amino acidsequence comprising residues 1 or about 26 to about 313 of FIG. 51 (SEQID NO:97).

In another aspect, the invention concerns an isolated PRO536polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 26 to about 313, inclusive of FIG. 51 (SEQ ID NO:97).

In a further aspect, the invention concerns an isolated PRO536polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 26 to about 313, inclusive of FIG. 51 (SEQ ID NO:97).

In yet another aspect, the invention concerns an isolated PRO536polypeptide, comprising the sequence of amino acid residues 1 or about26 to about 313, inclusive of FIG. 51 (SEQ ID NO:97), or a fragmentthereof sufficient to provide a binding site for an anti-PRO536antibody. Preferably, the PRO536 fragment retains a qualitativebiological activity of a native PRO536 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO536 polypeptide having the sequence ofamino acid residues from about 1 or about 26 to about 313, inclusive ofFIG. 51 (SEQ ID NO:97), or (b) the complement of the DNA molecule of(a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

21. PRO535

A cDNA clone (DNA49143-1429) has been identified, having homology tonucleic acid encoding a putative peptidyl-prolyl isomerase that encodesa novel polypeptide, designated in the present application as “PRO535”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO535 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO535 polypeptide having the sequence of amino acid residuesfrom about 1 or about 26 to about 201, inclusive of FIG. 53 (SEQ IDNO:99), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO535 polypeptide comprising DNA hybridizing to thecomplement of the nucleic acid between about nucleotides 78 or about 153and about 680, inclusive, of FIG. 52 (SEQ ID NO:98). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203013(DNA49143-1429) or (b) the complement of the nucleic acid molecule of(a). In a preferred embodiment, the nucleic acid comprises a DNAencoding the same mature polypeptide encoded by the human protein cDNAin ATCC Deposit No. 203013 (DNA49143-1429).

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 26 to about 201, inclusive of FIG. 53 (SEQ IDNO:99), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least 10 nucleotides and produced by hybridizing atest DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO535 polypeptide having the sequence of amino acid residuesfrom 1 or about 26 to about 201, inclusive of FIG. 53 (SEQ ID NO:99), or(b) the complement of the DNA molecule of (a), and, if the DNA moleculehas at least about an 80% sequence identity, preferably at least aboutan 85% sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO535 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, and itssoluble, i.e., transmembrane domain deleted or inactivated variants, oris complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from about aminoacid position 1 to about amino acid position 25 in the sequence of FIG.53 (SEQ ID NO:99). The transmembrane domain has been tentativelyidentified as extending from about amino acid position 155 to aboutamino acid position 174 in the PRO535 amino acid sequence (FIG. 53, SEQID NO:99).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 26 to about 201, inclusive of FIG. 53 (SEQ ID NO:99), or (b)the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO535 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 52 (SEQ ID NO:98).

In another embodiment, the invention provides isolated PRO535polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO535 polypeptide, which in certain embodiments, includes an amino acidsequence comprising residues 1 or about 26 to about 201 of FIG. 53 (SEQID NO:99).

In another aspect, the invention concerns an isolated PRO535polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 26 to about 201, inclusive of FIG. 53 (SEQ ID NO:99).

In a further aspect, the invention concerns an isolated PRO535polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 26 to about 201, inclusive of FIG. 53 (SEQ ID NO:99).

In yet another aspect, the invention concerns an isolated PRO535polypeptide, comprising the sequence of amino acid residues 1 or about26 to about 201, inclusive of FIG. 53 (SEQ ID NO:99), or a fragmentthereof sufficient to provide a binding site for an anti-PRO535antibody. Preferably, the PRO535 fragment retains a qualitativebiological activity of a native PRO535 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO535 polypeptide having the sequence ofamino acid residues from about 1 or about 26 to about 201, inclusive ofFIG. 53 (SEQ ID NO:99), or (b) the complement of the DNA molecule of(a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of a native PRO535 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO535 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO535 polypeptide by contacting thenative PRO535 polypeptide with a candidate molecule and monitoring abiological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO535 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

In another embodiment, the invention provides an expressed sequence tag(EST) designated herein as DNA30861 comprising the nucleotide sequenceof FIG. 54 (SEQ ID NO:100).

In another embodiment, the invention provides an expressed sequence tag(EST) designated herein as DNA36351 comprising the nucleotide sequenceof FIG. 55 (SEQ ID NO:101).

22. PRO718

Applicants have identified a cDNA clone that encodes a novel tetraspanmembrane polypeptide, wherein the polypeptide is designated in thepresent application as “PRO718”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO718 polypeptide. In one aspect,the isolated nucleic acid comprises DNA encoding the PRO718 polypeptidehaving amino acid residues 1 to 157 of FIG. 57 (SEQ ID NO:103), or iscomplementary to such encoding nucleic acid sequence, and remains stablybound to it under at least moderate, and optionally, under highstringency conditions. In other aspects, the isolated nucleic acidcomprises DNA encoding the PRO718 polypeptide having amino acid residuesX to 157 of FIG. 57 (SEQ ID NO:103), where X is any amino acid from 143to 152 of FIG. 57 (SEQ ID NO:103), or is complementary to such encodingnucleic acid sequence, and remains stably bound to it under at leastmoderate, and optionally, under high stringency conditions. The isolatednucleic acid sequence may comprise the cDNA insert of the DNA49647-1398vector deposited on Jun. 2, 1998 as ATCC 209919 which includes thenucleotide sequence encoding PRO718.

In another embodiment, the invention provides isolated PRO718polypeptide. In particular, the invention provides isolated nativesequence PRO718 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 to 157 of FIG. 57 (SEQ ID NO:103).Additional embodiments of the present invention are directed to isolatedPRO718 polypeptides comprising amino acids X to 157 of FIG. 57 (SEQ IDNO:103), where X is any amino acid from 143 to 152 of FIG. 57 (SEQ IDNO:103). Optionally, the PRO718 polypeptide is obtained or is obtainableby expressing the polypeptide encoded by the cDNA insert of theDNA49647-1398 vector deposited on Jun. 2, 1998 as ATCC 209919.

In another embodiment, the invention provides an expressed sequence tag(EST) designated herein as DNA15386 which comprises the nucleotidesequence of FIG. 58 (SEQ ID NO:104).

In another embodiment, the invention provides an expressed sequence tag(EST) designated herein as DNA 16630 which comprises the nucleotidesequence of FIG. 59 (SEQ ID NO:105).

In another embodiment, the invention provides an expressed sequence tag(EST) designated herein as DNA16829 which comprises the nucleotidesequence of FIG. 60 (SEQ ID NO:106).

In another embodiment, the invention provides an expressed sequence tag(EST) designated herein as DNA28357 which comprises the nucleotidesequence of FIG. 61 (SEQ ID NO:107).

In another embodiment, the invention provides an expressed sequence tag(EST) designated herein as DNA43512 which comprises the nucleotidesequence of FIG. 62 (SEQ ID NO:108).

23. PRO872

Applicants have identified a cDNA clone, DNA49819-1439, that encodes anovel polypeptide having homology to dehydrogenases wherein thepolypeptide is designated in the present application as “PRO872”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO872 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO872 polypeptide having the sequence of amino acid residuesfrom 1 or about 19 to about 610, inclusive of FIG. 64 (SEQ ID NO:113),or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO872 polypeptide comprising DNA that hybridizes tothe complement of the nucleic acid between about residues 68 and about1843, inclusive of FIG. 63 (SEQ ID NO:112). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 209931(DNA49819-1439), which was deposited on Jun. 2, 1998. In a preferredembodiment, the nucleic acid comprises a DNA molecule encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.209931 (DNA49819-1439).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 19 to about 610, inclusive of FIG. 64 (SEQ IDNO:113).

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO872 extracellular domain (ECD),with or without the N-terminal signal sequence and/or the initiatingmethionine, and its soluble variants (i.e. transmembrane domain(s)deleted or inactivated) or is complementary to such encoding nucleicacid molecule. The signal peptide has been tentatively identified asextending from amino acid position 1 to about amino acid position 18 inthe sequence of FIG. 64 (SEQ ID NO:113). The first transmembrane domainregion has been tentatively identified as extending from about aminoacid position 70 to about amino acid position 87 in the PRO872 aminoacid sequence (FIG. 64, SEQ ID NO:113).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA encoding a polypeptide scoring at least about80% positives, preferably at least about 90% positives, most preferablyat least about 95% positives when compared with the amino acid sequenceof residues 1 or about 19 to about 610, inclusive of FIG. 64 (SEQ IDNO:113).

Another embodiment is directed to fragments of a PRO872 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO872polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO872 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 or about 19 to 610 of FIG. 64 (SEQ IDNO:113).

In another aspect, the invention concerns an isolated PRO872polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 19 to 610, inclusive of FIG. 64 (SEQ ID NO:113).

In a further aspect, the invention concerns an isolated PRO872polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 19 to 610 of FIG. 64 (SEQ ID NO:113).

In another aspect, the invention concerns a PRO872 extracellular domaincomprising an amino acid sequence having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 19 to X of FIG. 64 (SEQ ID NO:113), wherein X is any one ofamino acid residues 66 to 75 of FIG. 64 (SEQ ID NO:113).

In yet another aspect, the invention concerns an isolated PRO872polypeptide, comprising the sequence of amino acid residues 1 or about19 to about 610, inclusive of FIG. 64 (SEQ ID NO:113), or a fragmentthereof sufficient to provide a binding site for an anti-PRO872antibody. Preferably, the PRO872 fragment retains a qualitativebiological activity of a native PRO872 polypeptide.

In another aspect, the present invention is directed to fragments of aPRO872 polypeptide which are sufficiently long to provide an epitopeagainst which an antibody may be generated.

In yet another embodiment, the invention concerns agonist andantagonists of the PRO872 polypeptide. In a particular embodiment, theagonist or antagonist is an anti-PRO872 antibody.

In a further embodiment, the invention concerns screening assays toidentify agonists or antagonists of a native PRO872 polypeptide.

In still a further embodiment, the invention concerns a compositioncomprising a PRO872 polypeptide as hereinabove defined, in combinationwith a pharmaceutically acceptable carrier.

24. PRO1063

Applicants have identified a cDNA clone that encodes a novel polypeptidehaving homology to human type IV collagenase, wherein the polypeptide isdesignated in the present application as “PRO1063”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1063 polypeptide. In one aspect,the isolated nucleic acid comprises DNA encoding the PRO1063 polypeptidehaving amino acid residues 1 to 301 of FIG. 66 (SEQ ID NO:115), or iscomplementary to such encoding nucleic acid sequence, and remains stablybound to it under at least moderate, and optionally, under highstringency conditions. In other aspects, the isolated nucleic acidcomprises DNA encoding the PRO1063 polypeptide having amino acidresidues about 22 to 301 of FIG. 66 (SEQ ID NO:115), or is complementaryto such encoding nucleic acid sequence, and remains stably bound to itunder at least moderate, and optionally, under high stringencyconditions. The isolated nucleic acid sequence may comprise the cDNAinsert of the DNA49820-1427 vector deposited on Jun. 2, 1998 as ATCC209932 which includes the nucleotide sequence encoding PRO1063.

In another embodiment, the invention provides isolated PRO1063polypeptide. In particular, the invention provides isolated nativesequence PRO1063 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 to 301 of FIG. 66 (SEQ ID NO:115).Additional embodiments of the present invention are directed to PRO1063polypeptides comprising amino acids about 22 to 301 of FIG. 66 (SEQ IDNO:115). Optionally, the PRO1063 polypeptide is obtained or isobtainable by expressing the polypeptide encoded by the cDNA insert ofthe DNA49820-1427 vector deposited on Jun. 2, 1998 as ATCC 209932.

25. PRO619

A cDNA clone (DNA49821-1562) has been identified that encodes a novelpolypeptide, designated in the present application as “PRO619.” PRO619polypeptides have sequence identity with VpreB genes, particularly toVpreB3.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO619 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO619 polypeptide having the sequence of amino acid residuesfrom about 1 or 21 to about 123, inclusive of FIG. 68 (SEQ ID NO:117),or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO619 polypeptide comprising DNA hybridizing to thecomplement of the nucleic acid between about residues 81 or 141 andabout 449, inclusive, of FIG. 67 (SEQ ID NO:116). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 209981(DNA49821-1562), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.209981 (DNA49821-1562).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 1 or 21 to about 123, inclusive of FIG. 68 (SEQID NO:117), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule produced by hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO619 polypeptide havingthe sequence of amino acid residues from about 1 or 21 to about 123,inclusive of FIG. 68 (SEQ ID NO:117), or (b) the complement of the DNAmolecule of (a), and, if the DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), isolating the testDNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO619 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, whichis in a soluble form. The signal peptide has been tentatively identifiedas extending from amino acid position 1 through about amino acidposition 20 in the sequence of FIG. 68 (SEQ ID NO:117).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 21 to about 123, inclusive of FIG. 68 (SEQ ID NO:117), or (b) thecomplement of the DNA of (a).

Another embodiment is directed to fragments of a PRO619 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 40 through about 80 nucleotides in length,preferably from about 20 through about 60 nucleotides in length, morepreferably from about 20 through about 50 nucleotides in length, andmost preferably from about 20 through about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO619polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO619 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 or 21 through 123 of FIG. 68 (SEQ IDNO:117).

In another aspect, the invention concerns an isolated PRO619polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 21 through about 123, inclusive of FIG. 68 (SEQ ID NO:117).

In a further aspect, the invention concerns an isolated PRO619polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 21through 123 of FIG. 68 (SEQ ID NO:117).

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO619 polypeptide having the sequence ofamino acid residues from about 1 or 21 to about 123, inclusive of FIG.68 (SEQ ID NO:117), or (b) the complement of the DNA molecule of (a),and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO619 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO619 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO619 polypeptide, by contactingthe native PRO619 polypeptide with a candidate molecule and monitoring abiological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO619 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

26. PRO943

A cDNA clone (DNA52192-1369) has been identified, having homology tonucleic acid encoding fibroblast growth factor receptor-4 that encodes anovel polypeptide, designated in the present application as “PRO943”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO943 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO943 polypeptide having the sequence of amino acid residuesfrom about 1 or about 18 to about 504, inclusive of FIG. 70 (SEQ IDNO:119), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO943 polypeptide comprising DNA hybridizing to thecomplement of the nucleic acid between about nucleotides 150 or about201 and about 1661, inclusive, of FIG. 69 (SEQ ID NO:118). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203042(DNA52192-1369) or (b) the complement of the nucleic acid molecule of(a). In a preferred embodiment, the nucleic acid comprises a DNAencoding the same mature polypeptide encoded by the human protein cDNAin ATCC Deposit No. 203042 (DNA52192-1369).

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 18 to about 504, inclusive of FIG. 70 (SEQ IDNO:119), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least 10 nucleotides and produced by hybridizing atest DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO943 polypeptide having the sequence of amino acid residuesfrom 1 or about 18 to about 504, inclusive of FIG. 70 (SEQ ID NO:119),or (b) the complement of the DNA molecule of (a), and, if the DNAmolecule has at least about an 80% sequence identity, preferably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO943 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, and itssoluble, i.e., transmembrane domain deleted or inactivated variants, oris complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from about aminoacid position 1 to about amino acid position 17 in the sequence of FIG.70 (SEQ ID NO:119). The transmembrane domain has been tentativelyidentified as extending from about amino acid position 376 to aboutamino acid position 396 in the PRO943 amino acid sequence (FIG. 70, SEQID NO:119).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 18 to about 504, inclusive of FIG. 70 (SEQ ID NO:119), or (b)the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO943 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 69 (SEQ ID NO:118).

In another embodiment, the invention provides isolated PRO943polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO943 polypeptide, which in certain embodiments, includes an amino acidsequence comprising residues 1 or about 18 to about 504 of FIG. 70 (SEQID NO:119).

In another aspect, the invention concerns an isolated PRO943polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 18 to about 504, inclusive of FIG. 70 (SEQ ID NO:119).

In a further aspect, the invention concerns an isolated PRO943polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 18 to about 504, inclusive of FIG. 70 (SEQ ID NO:119).

In yet another aspect, the invention concerns an isolated PRO943polypeptide, comprising the sequence of amino acid residues 1 or about18 to about 504, inclusive of FIG. 70 (SEQ ID NO:119), or a fragmentthereof sufficient to provide a binding site for an anti-PRO943antibody. Preferably, the PRO943 fragment retains a qualitativebiological activity of a native PRO943 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO943 polypeptide having the sequence ofamino acid residues from about 1 or about 18 to about 504, inclusive ofFIG. 70 (SEQ ID NO:119), or (b) the complement of the DNA molecule of(a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of a native PRO943 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO943 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO943 polypeptide by contacting thenative PRO943 polypeptide with a candidate molecule and monitoring abiological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO943 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

27. PRO1188

A cDNA clone (DNA52598-1518) has been identified that encodes a novelpolypeptide having homology to nucleotide pyrophosphohydrolase anddesignated in the present application as “PRO1188.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1188 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1188 polypeptide having the sequence of amino acidresidues from about 22 to about 1184, inclusive of FIG. 72 (SEQ IDNO:124), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1188 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 199 and about3687, inclusive, of FIG. 71 (SEQ ID NO:123). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203107(DNA52598-1518), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203107 (DNA52598-1518).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 22 to about 1184, inclusive of FIG. 72 (SEQ IDNO:124), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least about 50 nucleotides, and preferably at leastabout 100 nucleotides and produced by hybridizing a test DNA moleculeunder stringent conditions with (a) a DNA molecule encoding a PRO1188polypeptide having the sequence of amino acid residues from about 22 toabout 1184, inclusive of FIG. 72 (SEQ ID NO:124), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least aboutan 80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1188 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, or iscomplementary to such encoding nucleic acid molecule. The signal peptidehas been tentatively identified as extending from amino acid position 1through about amino acid position 21 in the sequence of FIG. 72 (SEQ IDNO:124).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 22to about 1184, inclusive of FIG. 72 (SEQ ID NO:124), or (b) thecomplement of the DNA of (a).

In another embodiment, the invention provides isolated PRO1188polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1188 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 22 to 1184 of FIG. 72 (SEQ ID NO:124).

In another aspect, the invention concerns an isolated PRO1188polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues22 to about 1184, inclusive of FIG. 72 (SEQ ID NO:124).

In a further aspect, the invention concerns an isolated PRO1188polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 22 to1184 of FIG. 72 (SEQ ID NO:124).

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1188 polypeptide having the sequence ofamino acid residues from about 22 to about 1184, inclusive of FIG. 72(SEQ ID NO:124), or (b) the complement of the DNA molecule of (a), andif the test DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1188 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1188 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1188 polypeptide, by contactingthe native PRO1188 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1188 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

28. PRO1133

A cDNA clone (DNA53913-1490) has been identified that encodes a novelpolypeptide having sequence identity with netrin-1a and designated inthe present application as “PRO1133.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1133 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1133 polypeptide having the sequence of amino acidresidues from about 19 to about 438, inclusive of FIG. 74 (SEQ IDNO:129), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1133 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 320 and about1579, inclusive, of FIG. 73 (SEQ ID NO:128). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203162(DNA53913-1490), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203162 (DNA53913-1490).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 19 to about 438, inclusive of FIG. 74 (SEQ IDNO:129), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least about 50 nucleotides, and preferably at leastabout 100 nucleotides and produced by hybridizing a test DNA moleculeunder stringent conditions with (a) a DNA molecule encoding a PRO1133polypeptide having the sequence of amino acid residues from about 19 toabout 438, inclusive of FIG. 74 (SEQ ID NO:129), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least aboutan 80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 19to about 438, inclusive of FIG. 74 (SEQ ID NO:129), or (b) thecomplement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1133 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1133polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1133 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 19 through 438 of FIG. 74 (SEQ ID NO:129).

In another aspect, the invention concerns an isolated PRO1133polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues19 to about 438, inclusive of FIG. 74 (SEQ ID NO:129).

In a further aspect, the invention concerns an isolated PRO1133polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 19through 438 of FIG. 74 (SEQ ID NO:129).

In yet another aspect, the invention concerns an isolated PRO1133polypeptide, comprising the sequence of amino acid residues 19 to about438, inclusive of FIG. 74 (SEQ ID NO:129), or a fragment thereofsufficient to provide a binding site for an anti-PRO1133 antibody.Preferably, the PRO1133 fragment retains a qualitative biologicalactivity of a native PRO1133 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1133 polypeptide having the sequence ofamino acid residues from about 19 to about 438, inclusive of FIG. 74(SEQ ID NO:129), or (b) the complement of the DNA molecule of (a), andif the test DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1133 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1133 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1133 polypeptide, by contactingthe native PRO1133 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1133 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

29. PRO784

A cDNA clone (DNA53978-1443) has been identified that encodes a novelpolypeptide, designated in the present application as “PRO784”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO784 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO784 polypeptide having the sequence of amino acid residuesfrom about 16 to about 228, inclusive of FIG. 76 (SEQ ID NO:135), or (b)the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO784 polypeptide comprising DNA hybridizing to thecomplement of the nucleic acid between about residues 182 and about 820,inclusive, of FIG. 75 (SEQ ID NO:134). Preferably, hybridization occursunder stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 209983(DNA53978-1443), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.209983 (DNA53978-1443).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 16 to about 228, inclusive of FIG. 76 (SEQ IDNO:135), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least 50, and preferably at least 100 nucleotides andproduced by hybridizing a test DNA molecule under stringent conditionswith (a) a DNA molecule encoding a PRO784 polypeptide having thesequence of amino acid residues from about 16 to about 228, inclusive ofFIG. 76 (SEQ ID NO:135), or (b) the complement of the DNA molecule of(a), and, if the DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), isolating the testDNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO784 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, and itssoluble, i.e. transmembrane domain deleted or inactivated variants, oris complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from amino acidposition about 1 to about amino acid position 15 in the sequence of FIG.76 (SEQ ID NO:135). The first transmembrane domain has been tentativelyidentified as extending from about amino acid position 68 to about aminoacid position 87 in the PRO784 amino acid sequence (FIG. 76, SEQ IDNO:135).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 16to about 228, inclusive of FIG. 76 (SEQ ID NO:135), or (b) thecomplement of the DNA of (a).

In another aspect, the invention concerns hybridization probes thatcomprise fragments of the PRO784 coding sequence, or complementarysequence thereof. The hybridization probes preferably have at leastabout 20 nucleotides to about 80 nucleotides, and more preferably, atleast about 40 to about 80 nucleotides.

In another embodiment, the invention provides isolated PRO784polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO784 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 16 to 228 of FIG. 76 (SEQ ID NO:135).

In another aspect, the invention concerns an isolated PRO784polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues16 to about 228, inclusive of FIG. 76 (SEQ ID NO:135).

In a further aspect, the invention concerns an isolated PRO784polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 16 to228 of FIG. 76 (SEQ ID NO:135).

In yet another aspect, the invention concerns an isolated PRO784polypeptide, comprising the sequence of amino acid residues 16 to about228, inclusive of FIG. 76 (SEQ ID NO:135), or a fragment thereofsufficient to provide a binding site for an anti-PRO784 antibody.Preferably, the PRO784 fragment retains a qualitative biologicalactivity of a native PRO784 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO784 polypeptide having the sequence ofamino acid residues from about 16 to about 228, inclusive of FIG. 76(SEQ ID NO:135), or (b) the complement of the DNA molecule of (a), andif the test DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO784 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO784 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO784 polypeptide, by contactingthe native PRO784 polypeptide with a candidate molecule and monitoring abiological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO784 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

30. PRO783

Applicants have identified a cDNA clone that encodes a novel multi-spantransmembrane polypeptide, wherein the polypeptide is designated in thepresent application as “PRO783”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO783 polypeptide. In one aspect,the isolated nucleic acid comprises DNA encoding the PRO783 polypeptidehaving amino acid residues 1 to 489 of FIG. 79 (SEQ ID NO:138), or iscomplementary to such encoding nucleic acid sequence, and remains stablybound to it under at least moderate, and optionally, under highstringency conditions. In other aspects, the isolated nucleic acidcomprises DNA encoding the PRO783 polypeptide having amino acid residues1 to X of FIG. 79 (SEQ ID NO:138), where X is any amino acid from 19 to28 of FIG. 79 (SEQ ID NO:138), or is complementary to such encodingnucleic acid sequence, and remains stably bound to it under at leastmoderate, and optionally, under high stringency conditions. The isolatednucleic acid sequence may comprise the cDNA insert of the DNA53996-1442vector deposited on Jun. 2, 1998 as ATCC 209921 which includes thenucleotide sequence encoding PRO783.

In another embodiment, the invention provides isolated PRO783polypeptide. In particular, the invention provides isolated nativesequence PRO783 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 to 489 of FIG. 79 (SEQ ID NO:138).Additional embodiments of the present invention are directed to PRO783polypeptides comprising amino acid 1 to about X of FIG. 79 (SEQ IDNO:138), where X is any amino acid from 19 to 28 of FIG. 79 (SEQ IDNO:138). Optionally, the PRO783 polypeptide is obtained or is obtainableby expressing the polypeptide encoded by the cDNA insert of theDNA53996-1442 vector deposited on Jun. 2, 1998, as ATCC 209921.

In another embodiment, the invention provides an expressed sequence tag(EST) designated herein as DNA45201 which comprises the nucleic acidsequence shown in FIG. 80 (SEQ ID NO:139).

In another embodiment, the invention provides an expressed sequence tag(EST) designated herein as DNA14575 which comprises the nucleic acidsequence shown in FIG. 81 (SEQ ID NO:140).

31. PRO820

A cDNA clone (DNA56041-1416) has been identified, having sequenceidentity with immunoglobulin gamma Fc receptors that encodes a novelpolypeptide, designated in the present application as “PRO820”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO820 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO820 polypeptide having the sequence of amino acid residuesfrom about 1 or 16 to about 124, inclusive of FIG. 83 (SEQ ID NO:146),or (b) the complement of the DNA molecule of (a). The term “or” as usedherein to refer to amino or nucleic acids is meant to refer to twoalternative embodiments provided herein, i.e., 1–124, or in anotherembodiment, 16–124.

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO820 polypeptide comprising DNA hybridizing to thecomplement of the nucleic acid between about residues 115 or 160 andabout 486, inclusive, of FIG. 82 (SEQ ID NO:145). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203021(DNA56041-1416), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.(DNA56041-1416).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 1 or 16 to about 124, inclusive of FIG. 83 (SEQID NO:146), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule produced by hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO820 polypeptide havingthe sequence of amino acid residues from about 1 or 16 to about 124,inclusive of FIG. 83 (SEQ ID NO:146), or (b) the complement of the DNAmolecule of (a), and, if the DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), isolating the testDNA molecule.

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 16 to about 124, inclusive of FIG. 83 (SEQ ID NO:146), or (b) thecomplement of the DNA of (a).

In another embodiment, the invention provides isolated PRO820polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO820 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 or 16 through 124 of FIG. 83 (SEQ IDNO:146).

In another aspect, the invention concerns an isolated PRO820polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 16 to about 124, inclusive of FIG. 83 (SEQ ID NO:146).

In a further aspect, the invention concerns an isolated PRO820polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 16through 124 of FIG. 83 (SEQ ID NO:146).

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO820 polypeptide having the sequence ofamino acid residues from about 1 or 16 to about 124, inclusive of FIG.83 (SEQ ID NO:146), or (b) the complement of the DNA molecule of (a),and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO820 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO820 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO820 polypeptide, by contactingthe native PRO820 polypeptide with a candidate molecule and monitoring abiological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO820 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

32. PRO1080

A cDNA clone (DNA56047-1456) has been identified that encodes a novelpolypeptide, designated in the present application as “PRO1080.” PRO1080polypeptides have sequence identity with DnaJ proteins.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1080 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1080 polypeptide having the sequence of amino acidresidues from about 1 or 23 to about 358, inclusive of FIG. 85 (SEQ IDNO:148), or (b) the complement of the DNA molecule of (a). The term “or”as used herein to refer to amino or nucleic acids is meant to refer totwo alternative embodiments provided herein, i.e., 1–358, or in anotherembodiment, 23–358.

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1080 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 159 or 225 andabout 1232, inclusive, of FIG. 84 (SEQ ID NO:147). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 209948(DNA56047-1456), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.209948 (DNA56047-1456).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 1 or 23 to about 358, inclusive of FIG. 85 (SEQID NO:148), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule produced by hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1080 polypeptide havingthe sequence of amino acid residues from about 1 or 23 to about 358,inclusive of FIG. 85 (SEQ ID NO:148), or (b) the complement of the DNAmolecule of (a), and, if the DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), isolating the testDNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1080 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine. Thesignal peptide has been tentatively identified as extending from aminoacid position 1 through about amino acid position 22 in the sequence ofFIG. 85 (SEQ ID NO:148).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 23 to about 358, inclusive of FIG. 85 (SEQ ID NO:148), or (b) thecomplement of the DNA of (a).

In another embodiment, the invention provides isolated PRO1080polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1080 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 or 23 through 358 of FIG. 85 (SEQ IDNO:148).

In another aspect, the invention concerns an isolated PRO1080polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 23 to about 358, inclusive of FIG. 85 (SEQ ID NO:148).

In a further aspect, the invention concerns an isolated PRO1080polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 23through 358 of FIG. 85 (SEQ ID NO:148).

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1080 polypeptide having the sequence ofamino acid residues from about 1 or 23 to about 358, inclusive of FIG.85 (SEQ ID NO:148), or (b) the complement of the DNA molecule of (a),and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1080 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1080 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1080 polypeptide, by contactingthe native PRO1080 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1080 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

In another embodiment, the invention provides an expressed sequence tag(EST) designated herein as DNA36527 comprising the nucleotide sequenceof FIG. 86 (SEQ ID NO:149).

33. PRO1079

A cDNA clone (DNA56050-1455) has been identified that encodes a novelpolypeptide, designated in the present application as “PRO1079”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1079 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1079 polypeptide having the sequence of amino acidresidues from about 30 to about 226, inclusive of FIG. 88 (SEQ IDNO:151), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1079 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 270 and about860, inclusive, of FIG. 87 (SEQ ID NO:150). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203011(DNA56050-1455), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203011 (DNA56050-1455).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 30 to about 226, inclusive of FIG. 88 (SEQ IDNO:151), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least about 50 nucleotides and preferably at leastabout 100 nucleotides, and produced by hybridizing a test DNA moleculeunder stringent conditions with (a) a DNA molecule encoding a PRO1079polypeptide having the sequence of amino acid residues from about 30 toabout 226, inclusive of FIG. 88 (SEQ ID NO:151), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least aboutan 80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1079 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine. Thesignal peptide has been tentatively identified as extending from aminoacid position 1 through about amino acid position 29 in the sequence ofFIG. 88 (SEQ ID NO:151).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 30to about 226, inclusive of FIG. 88 (SEQ ID NO:151), or (b) thecomplement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1079 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1079polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1079 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 30 to 226 of FIG. 88 (SEQ ID NO:151).

In another aspect, the invention concerns an isolated PRO1079polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues30 to about 226, inclusive of FIG. 88 (SEQ ID NO:151).

In a further aspect, the invention concerns an isolated PRO1079polypeptide,comprising an amino acid sequence scoring at least about 80%positives, preferably at least about 85% positives, more preferably atleast about 90% positives, most preferably at least about 95% positiveswhen compared with the amino acid sequence of residues 30 to 226 of FIG.88 (SEQ ID NO:151).

In yet another aspect, the invention concerns an isolated PRO1079polypeptide, comprising the sequence of amino acid residues 30 to about226, inclusive of FIG. 88 (SEQ ID NO:151), or a fragment thereofsufficient to provide a binding site for an anti-PRO1079 antibody.Preferably, the PRO1079 fragment retains a qualitative biologicalactivity of a native PRO1079 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1079 polypeptide having the sequence ofamino acid residues from about 30 to about 226, inclusive of FIG. 88(SEQ ID NO:151), or (b) the complement of the DNA molecule of (a), andif the test DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

34. PRO793

A cDNA clone (DNA56110-1437) has been identified that encodes a noveltransmembrane polypeptide, designated in the present application as“PRO793”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO793 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO793 polypeptide having the sequence of amino acid residuesfrom about 1 to about 138, inclusive of FIG. 90 (SEQ ID NO:153), or (b)the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO793 polypeptide comprising DNA hybridizing to thecomplement of the nucleic acid between about nucleotides 77 and about490, inclusive, of FIG. 89 (SEQ ID NO:152). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203113(DNA56110-1437) or (b) the complement of the nucleic acid molecule of(a). In a preferred embodiment, the nucleic acid comprises a DNAencoding the same mature polypeptide encoded by the human protein cDNAin ATCC Deposit No. 203113 (DNA56110-1437).

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 to about 138, inclusive of FIG. 90 (SEQ ID NO:153), or(b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least 10 nucleotides and produced by hybridizing atest DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO793 polypeptide having the sequence of amino acid residuesfrom 1 to about 138, inclusive of FIG. 90 (SEQ ID NO:153), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO793 polypeptide, with or withoutthe initiating methionine, and its soluble, i.e., transmembrane domaindeleted or inactivated variants, or is complementary to such encodingnucleic acid molecule. The transmembrane domains have been tentativelyidentified as extending from about amino acid position 12 to about aminoacid position 30, from about amino acid position 33 to about amino acidposition 52, from about amino acid position 69 to about amino acidposition 89 and from about amino acid position 93 to about amino acidposition 109 in the PRO793 amino acid sequence (FIG. 90, SEQ ID NO:153).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1to about 138, inclusive of FIG. 90 (SEQ ID NO:153), or (b) thecomplement of the DNA of (a).

Another embodiment is directed to fragments of a PRO793 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 89 (SEQ ID NO:152).

In another embodiment, the invention provides isolated PRO793polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO793 polypeptide, which in certain embodiments, includes an amino acidsequence comprising residues 1 to about 138 of FIG. 90 (SEQ ID NO:153).

In another aspect, the invention concerns an isolated PRO793polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 to about 138, inclusive of FIG. 90 (SEQ ID NO:153).

In a further aspect, the invention concerns an isolated PRO793polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 toabout 138, inclusive of FIG. 90 (SEQ ID NO:153).

In yet another aspect, the invention concerns an isolated PRO793polypeptide, comprising the sequence of amino acid residues 1 to about138, inclusive of FIG. 90 (SEQ ID NO:153), or a fragment thereofsufficient to provide a binding site for an anti-PRO793 antibody.Preferably, the PRO793 fragment retains a qualitative biologicalactivity of a native PRO793 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO793 polypeptide having the sequence ofamino acid residues from about 1 to about 138, inclusive of FIG. 90 (SEQID NO:153), or (b) the complement of the DNA molecule of (a), and if thetest DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In another embodiment, the invention provides an expressed sequence tag(EST) designated herein as DNA50177 comprising the nucleotide sequenceof FIG. 91 (SEQ ID NO:154).

35. PRO1016

A cDNA clone (DNA56113-1378) has been identified, having sequenceidentity with acyltransferases that encodes a novel polypeptide,designated in the present application as “PRO1016”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1016 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1016 polypeptide having the sequence of amino acidresidues from about 1 or 19 to about 378, inclusive of FIG. 93 (SEQ IDNO:156), or (b) the complement of the DNA molecule of (a). The term “or”as used herein to refer to amino or nucleic acids is meant to refer totwo alternative embodiments provided herein, i.e., 1–378, or in anotherembodiment, 19–378.

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1016 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 168 or 222 andabout 1301, inclusive, of FIG. 92 (SEQ ID NO:155). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203049(DNA56113-1378), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203049 (DNA56113-1378).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 1 or 19 to about 378, inclusive of FIG. 93 (SEQID NO:156), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule produced by hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1016 polypeptide havingthe sequence of amino acid residues from about 1 or 19 to about 378,inclusive of FIG. 93 (SEQ ID NO:156), or (b) the complement of the DNAmolecule of (a), and, if the DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), isolating the testDNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1016 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, and itssoluble, i.e. transmembrane domains deleted or inactivated variants, oris complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from amino acidposition 1 through about amino acid position 18 in the sequence of FIG.93 (SEQ ID NO:156). The transmembrane domains have been tentativelyidentified as extending from about amino acid position 305 through aboutamino acid position 330 and from about amino acid position 332 throughabout amino acid position 352 in the PRO1016 amino acid sequence (FIG.93, SEQ ID NO:156).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 19 to about 378, inclusive of FIG. 93 (SEQ ID NO:156), or (b) thecomplement of the DNA of (a).

In another embodiment, the invention provides isolated PRO1016polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1016 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 or 19 through 378 of FIG. 93 (SEQ IDNO:156).

In another aspect, the invention concerns an isolated PRO1016polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 19 to about 378, inclusive of FIG. 93 (SEQ ID NO:156).

In a further aspect, the invention concerns an isolated PRO1016polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 19through 378 of FIG. 93 (SEQ ID NO:156).

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1016 polypeptide having the sequence ofamino acid residues from about 1 or 19 to about 378, inclusive of FIG.93 (SEQ ID NO:156), or (b) the complement of the DNA molecule of (a),and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1016 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1016 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1016 polypeptide, by contactingthe native PRO1016 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1016 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

36. PRO1013

Applicants have identified a cDNA clone that encodes a novel polypeptidehaving sequence identity with P120, wherein the polypeptide isdesignated in the present application as “PRO1013”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1013 polypeptide. In one aspect,the isolated nucleic acid comprises DNA encoding the PRO1013 polypeptidehaving amino acid residues 1 through 409 of FIG. 95 (SEQ ID NO:158), oris complementary to such encoding nucleic acid sequence, and remainsstably bound to it under at least moderate, and optionally, under highstringency conditions. The isolated nucleic acid sequence may comprisethe cDNA insert of the vector deposited on Jun. 2, 1998 with the ATCC asDNA56410-1414 which includes the nucleotide sequence encoding PRO1013.

In another embodiment, the invention provides isolated PRO1013polypeptide. In particular, the invention provides isolated nativesequence PRO1013 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 through 409 of FIG. 95 (SEQ IDNO:158). Optionally, the PRO1013 polypeptide is obtained or isobtainable by expressing the polypeptide encoded by the cDNA insert ofthe vector deposited on Jun. 2, 1998 with the ATCC as DNA56410-1414.

37. PRO937

Applicants have identified a cDNA clone that encodes a novel polypeptidehaving homology to glypican family proteins, wherein the polypeptide isdesignated in the present application as “PRO937”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO937 polypeptide. In one aspect,the isolated nucleic acid comprises DNA encoding the PRO937 polypeptidehaving amino acid residues 1 to 556 of FIG. 97 (SEQ ID NO:160), or iscomplementary to such encoding nucleic acid sequence, and remains stablybound to it under at least moderate, and optionally, under highstringency conditions. In other aspects, the isolated nucleic acidcomprises DNA encoding the PRO937 polypeptide having amino acid residuesabout 23 to 556 of FIG. 97 (SEQ ID NO:160), or is complementary to suchencoding nucleic acid sequence, and remains stably bound to it under atleast moderate, and optionally, under high stringency conditions. Theisolated nucleic acid sequence may comprise the cDNA insert of theDNA56436-1448 vector deposited on May 27, 1998, as ATCC 209902 whichincludes the nucleotide sequence encoding PRO937.

In another embodiment, the invention provides isolated PRO937polypeptide. In particular, the invention provides isolated nativesequence PRO937 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 to 556 of FIG. 97 (SEQ ID NO:160).Additional embodiments of the present invention are directed to PRO937polypeptides comprising amino acids about 23 to 556 of FIG. 97 (SEQ IDNO:160). Optionally, the PRO937 polypeptide is obtained or is obtainableby expressing the polypeptide encoded by the cDNA insert of theDNA56436-1448 vector deposited on May 27, 1998 as ATCC 209902.

38. PRO842

A cDNA clone (DNA56855-1447) has been identified that encodes a novelsecreted polypeptide, designated in the present application as “PRO842.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO842 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO842 polypeptide having the sequence of amino acid residuesfrom about 23 to about 119, inclusive of FIG. 99 (SEQ ID NO:165), or (b)the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO842 polypeptide comprising DNA hybridizing to thecomplement of the nucleic acid between about residues 219 and about 509,inclusive, of FIG. 98 (SEQ ID NO:164). Preferably, hybridization occursunder stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203004(DNA56855-1447), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203004 (DNA56855-1447).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 23 to about 119, inclusive of FIG. 99 (SEQ IDNO:165), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least about 50 nucleotides, and preferably at leastabout 100 nucleotides, and produced by hybridizing a test DNA moleculeunder stringent conditions with (a) a DNA molecule encoding a PRO842polypeptide having the sequence of amino acid residues from about 23 toabout 119, inclusive of FIG. 99 (SEQ ID NO:165), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least aboutan 80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO842 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, and itssoluble, i.e. transmembrane domain deleted or inactivated variants, oris complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from amino acidposition 1 through about amino acid position 22 in the sequence of FIG.99 (SEQ ID NO:165).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 23to about 119, inclusive of FIG. 99 (SEQ ID NO:165), or (b) thecomplement of the DNA of (a).

Another embodiment is directed to fragments of a PRO842 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO842polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO842 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 23 to 119 of FIG. 99 (SEQ ID NO:165).

In another aspect, the invention concerns an isolated PRO842polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues23 to about 119, inclusive of FIG. 99 (SEQ ID NO:165).

In a further aspect, the invention concerns an isolated PRO842polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 23 to119 of FIG. 99 (SEQ ID NO:165).

In yet another aspect, the invention concerns an isolated PRO842polypeptide, comprising the sequence of amino acid residues 23 to about119, inclusive of FIG. 99 (SEQ ID NO:165), or a fragment thereofsufficient to provide a binding site for an anti-PRO842 antibody.Preferably, the PRO842 fragment retains a qualitative biologicalactivity of a native PRO842 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO842 polypeptide having the sequence ofamino acid residues from about 23 to about 119, inclusive of FIG. 99(SEQ ID NO:165), or (b) the complement of the DNA molecule of (a), andif the test DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

39. PRO839

A cDNA clone (DNA56859-1445) has been identified that encodes a novelpolypeptide, designated in the present application as “PRO839.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO839 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO839 polypeptide having the sequence of amino acid residuesfrom about 24 to about 87, inclusive of FIG. 101 (SEQ ID NO:167), or (b)the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO839 polypeptide comprising DNA hybridizing to thecomplement of the nucleic acid between about residues 71 and about 262,inclusive, of FIG. 100 (SEQ ID NO:166). Preferably, hybridization occursunder stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203019(DNA56859-1445), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203019 (DNA56859-1445).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 24 to about 87, inclusive of FIG. 101 (SEQ IDNO:167), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least 50 nucleotides, and preferably at least 100nucleotides and produced by hybridizing a test DNA molecule understringent conditions with (a) a DNA molecule encoding a PRO839polypeptide having the sequence of amino acid residues from about 24 toabout 87, inclusive of FIG. 101 (SEQ ID NO:167), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least aboutan 80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO839 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, and itssoluble, i.e. transmembrane domain deleted or inactivated variants, oris complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from amino acidposition 1 through about amino acid position 23 in the sequence of FIG.101 (SEQ ID NO:167).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 24to about 87, inclusive of FIG. 101 (SEQ ID NO:167), or (b) thecomplement of the DNA of (a).

Another embodiment is directed to fragments of a PRO839 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO839polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO839 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 24 to 87 of FIG. 101 (SEQ ID NO:167).

In another aspect, the invention concerns an isolated PRO839polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues24 to about 87, inclusive of FIG. 101 (SEQ ID NO:167).

In a further aspect, the invention concerns an isolated PRO839polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 24 to87 of FIG. 101 (SEQ ID NO:167).

In yet another aspect, the invention concerns an isolated PRO839polypeptide, comprising the sequence of amino acid residues 24 to about87, inclusive of FIG. 101 (SEQ ID NO:167), or a fragment thereofsufficient to provide a binding site for an anti-PRO839 antibody.Preferably, the PRO839 fragment retains a qualitative biologicalactivity of a native PRO839 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO839 polypeptide having the sequence ofamino acid residues from about 24 to about 87, inclusive of FIG. 101(SEQ ID NO:167), or (b) the complement of the DNA molecule of (a), andif the test DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

40. PRO1180

Applicants have identified a cDNA clone (DNA56860-1510) having homologyto nucleic acid encoding methyltransferase enzymes that encodes a novelpolypeptide, designated in the present application as “PRO1180”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1180 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1180 polypeptide having the sequence of amino acidresidues from about 1 or about 24 to about 277, inclusive of FIG. 103(SEQ ID NO:169), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1180 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about nucleotides 78 or about147 and about 908, inclusive of FIG. 102 (SEQ ID NO:168). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 209952(DNA56860-1510). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 209952 (DNA56860-1510).

A In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 24 to about 277, inclusive of FIG. 103 (SEQ IDNO:169).

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1180 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, or iscomplementary to such encoding nucleic acid molecule. The signal peptidehas been tentatively identified as extending from about amino acidposition 1 to about amino acid position 23 in the sequence of FIG. 103(SEQ ID NO:169).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA encoding a polypeptide scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 24 to about 277, inclusive of FIG. 103 (SEQ ID NO:169).

Another embodiment is directed to fragments of a PRO1180 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1180polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO1180 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 or about 24 to about 277 of FIG. 103 (SEQID NO:169).

In another aspect, the invention concerns an isolated PRO1180polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 24 to about 277, inclusive of FIG. 103 (SEQ ID NO:169).

In a further aspect, the invention concerns an isolated PRO1180polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 24 to about 277, inclusive of FIG. 103 (SEQ ID NO:169).

In yet another aspect, the invention concerns an isolated PRO1180polypeptide, comprising the sequence of amino acid residues 1 or about24 to about 277, inclusive of FIG. 103 (SEQ ID NO:169), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1180antibody. Preferably, the PRO1180 fragment retains a qualitativebiological activity of a native PRO1180 polypeptide.

In another aspect, the present invention is directed to fragments of aPRO1180 polypeptide which are sufficiently long to provide an epitopeagainst which an antibody may be generated.

In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1180 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1180 antibody.

In a further embodiment, the invention concerns screening assays toidentify agonists or antagonists of a native PRO1180 polypeptide.

In still a further embodiment, the invention concerns a compositioncomprising a PRO1180 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

41. PRO1134

A cDNA clone (DNA56865-1491) has been identified that encodes a novelsecreted polypeptide, designated in the present application as“PRO1134”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1134 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1134 polypeptide having the sequence of amino acidresidues from about 1 or about 24 to about 371, inclusive of FIG. 105(SEQ ID NO:171), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1134 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about nucleotides 153 orabout 222 and about 1265, inclusive, of FIG. 104 (SEQ ID NO:170).Preferably, hybridization occurs under stringent hybridization and washconditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203022(DNA56865-1491) or (b) the complement of the nucleic acid molecule of(a). In a preferred embodiment, the nucleic acid comprises a DNAencoding the same mature polypeptide encoded by the human protein cDNAin ATCC Deposit No. 203022 (DNA56865-1491).

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 24 to about 371, inclusive of FIG. 105 (SEQ IDNO:171), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least 10 nucleotides and produced by hybridizing atest DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1134 polypeptide having the sequence of amino acidresidues from 1 or about 24 to about 371, inclusive of FIG. 105 (SEQ IDNO:171), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, preferably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1134 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, or iscomplementary to such encoding nucleic acid molecule. The signal peptidehas been tentatively identified as extending from about amino acidposition 1 to about amino acid position 23 in the sequence of FIG. 105(SEQ ID NO:171).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 24 to about 371, inclusive of FIG. 105 (SEQ ID NO:171), or (b)the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1134 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 104 (SEQ ID NO:170).

In another embodiment, the invention provides isolated PRO1134polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO1134 polypeptide, which in certain embodiments, includes an aminoacid sequence comprising residues 1 or about 24 to about 371 of FIG. 105(SEQ ID NO:171).

In another aspect, the invention concerns an isolated PRO1134polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 24 to about 371, inclusive of FIG. 105 (SEQ ID NO:171).

In a further aspect, the invention concerns an isolated PRO1134polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 24 to about 371, inclusive of FIG. 105 (SEQ ID NO:171).

In yet another aspect, the invention concerns an isolated PRO1134polypeptide, comprising the sequence of amino acid residues 1 or about24 to about 371, inclusive of FIG. 105 (SEQ ID NO:171), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1134antibody. Preferably, the PRO1134 fragment retains a qualitativebiological activity of a native PRO1134 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1134 polypeptide having the sequence ofamino acid residues from about 1 or about 24 to about 371, inclusive ofFIG. 105 (SEQ ID NO:171), or (b) the complement of the DNA molecule of(a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In another embodiment, the invention provides an expressed sequence tag(EST) designated herein as DNA52352 comprising the nucleotide sequenceof SEQ ID NO:172 (see FIG. 106).

In another embodiment, the invention provides an expressed sequence tag(EST) designated herein as DNA55725 comprising the nucleotide sequenceof SEQ ID NO:173 (see FIG. 107).

42. PRO830

A cDNA clone (DNA56866-1342) has been identified that encodes a novelsecreted polypeptide, designated in the present application as “PRO830”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO830 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO830 polypeptide having the sequence of amino acid residuesfrom about 1 or about 34 to about 87, inclusive of FIG. 109 (SEQ IDNO:175), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO830 polypeptide comprising DNA hybridizing to thecomplement of the nucleic acid between about nucleotides 154 or about253 and about 414, inclusive, of FIG. 108 (SEQ ID NO:174). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203023(DNA56866-1342) or (b) the complement of the nucleic acid molecule of(a). In a preferred embodiment, the nucleic acid comprises a DNAencoding the same mature polypeptide encoded by the human protein cDNAin ATCC Deposit No. 203023 (DNA56866-1342).

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 34 to about 87, inclusive of FIG. 109 (SEQ IDNO:175), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least 10 nucleotides and produced by hybridizing atest DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO830 polypeptide having the sequence of amino acid residuesfrom 1 or about 34 to about 87, inclusive of FIG. 109 (SEQ ID NO:175),or (b) the complement of the DNA molecule of (a), and, if the DNAmolecule has at least about an 80% sequence identity, preferably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO830 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, or iscomplementary to such encoding nucleic acid molecule. The signal peptidehas been tentatively identified as extending from about amino acidposition 1 to about amino acid position 33 in the sequence of FIG. 109(SEQ ID NO:175).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 34 to about 87, inclusive of FIG. 109 (SEQ ID NO:175), or (b)the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO830 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 108 (SEQ ID NO:174).

In another embodiment, the invention provides isolated PRO830polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO830 polypeptide, which in certain embodiments, includes an amino acidsequence comprising residues 1 or about 34 to about 87 of FIG. 109 (SEQID NO:175).

In another aspect, the invention concerns an isolated PRO830polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 34 to about 87, inclusive of FIG. 109 (SEQ ID NO:175).

In a further aspect, the invention concerns an isolated PRO830polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 34 to about 87, inclusive of FIG. 109 (SEQ ID NO:175).

In yet another aspect, the invention concerns an isolated PRO830polypeptide, comprising the sequence of amino acid residues 1 or about34 to about 87, inclusive of FIG. 109 (SEQ ID NO:175), or a fragmentthereof sufficient to provide a binding site for an anti-PRO830antibody. Preferably, the PRO830 fragment retains a qualitativebiological activity of a native PRO830 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO830 polypeptide having the sequence ofamino acid residues from about 1 or about 34 to about 87, inclusive ofFIG. 109 (SEQ ID NO:175), or (b) the complement of the DNA molecule of(a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

43. PRO1115

A cDNA clone (DNA56868-1478) has been identified that encodes a noveltransmembrane polypeptide, designated in the present application as“PRO115”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1115 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1115 polypeptide having the sequence of amino acidresidues from about 21 to about 445, inclusive of FIG. 111 (SEQ IDNO:177), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1115 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 249 and about1523, inclusive, of FIG. 110 (SEQ ID NO:176). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203024(DNA56868-1478), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203024 (DNA56868-1478).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 21 to about 445, inclusive of FIG. 111 (SEQ IDNO:177), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least about 50 nucleotides and preferably at leastabout 100 nucleotides and produced by hybridizing a test DNA moleculeunder stringent conditions with (a) a DNA molecule encoding a PRO1115polypeptide having the sequence of amino acid residues from about 21 toabout 445, inclusive of FIG. 111 (SEQ ID NO:177), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least aboutan 80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1115 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, and oneor more of its transmembrane domains deleted or inactivated, or iscomplementary to such encoding nucleic acid molecule. The signal peptidehas been tentatively identified as extending from amino acid position 1through about amino acid position 20 in the sequence of FIG. 111 (SEQ IDNO:177). Transmembrane domains have been tentatively identified asextending from about amino acid positions 35–54, 75–97, 126–146,185–204, 333–350, and 352–371 in the PRO1115 amino acid sequence (FIG.111, SEQ ID NO:177).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 21to about 445, inclusive of FIG. 111 (SEQ ID NO:177), or (b) thecomplement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1115 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1115polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1115 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 21 to 445 of FIG. 111 (SEQ ID NO:177).

In another aspect, the invention concerns an isolated PRO1115polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues21 to about 445, inclusive of FIG. 111 (SEQ ID NO:177).

In a further aspect, the invention concerns an isolated PRO1115polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 21 to445 of FIG. 111 (SEQ ID NO:177).

In yet another aspect, the invention concerns an isolated PRO1115polypeptide, comprising the sequence of amino acid residues 21 to about445, inclusive of FIG. 111 (SEQ ID NO:177), or a fragment thereofsufficient to provide a binding site for an anti-PRO1115 antibody.Preferably, the PRO1115 fragment retains a qualitative biologicalactivity of a native PRO1115 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1115 polypeptide having the sequence ofamino acid residues from about 21 to about 445, inclusive of FIG. 111(SEQ ID NO:177), or (b) the complement of the DNA molecule of (a), andif the test DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

44. PRO1277

A cDNA clone (DNA56869-1545) has been identified that encodes a novelpolypeptide having homology to Coch-5B2 and designated in the presentapplication as “PRO1277.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1277 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1277 polypeptide having the sequence of amino acidresidues from about 27 to about 678, inclusive of FIG. 113 (SEQ IDNO:179), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1277 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 266 and about2221, inclusive, of FIG. 112 (SEQ ID NO:178). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203161(DNA56869-1545), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203161 (DNA56869-1545).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 27 to about 678, inclusive of FIG. 113 (SEQ IDNO:179), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least about 50 nucleotides, and preferably at leastabout 100 nucleotides and produced by hybridizing a test DNA moleculeunder stringent conditions with (a) a DNA molecule encoding a PRO1277polypeptide having the sequence of amino acid residues from about 27 toabout 678, inclusive of FIG. 113 (SEQ ID NO:179), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least aboutan 80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1277 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, and itssoluble, i.e. transmembrane domain deleted or inactivated variants, oris complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from amino acidposition 1 through about amino acid position 26 in the sequence of FIG.113 (SEQ ID NO:179). The transmembrane domain has been tentativelyidentified as extending from about amino acid position 181 to aboutamino acid position 200 in the PRO1277 amino acid sequence (FIG. 113,SEQ ID NO:179).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 27to about 678, inclusive of FIG. 113 (SEQ ID NO:179), or (b) thecomplement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1277 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1277polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1277 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 27 to 678 of FIG. 113 (SEQ ID NO:179).

In another aspect, the invention concerns an isolated PRO1277polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues27 to about 678, inclusive of FIG. 113 (SEQ ID NO:179).

In a further aspect, the invention concerns an isolated PRO1277polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 27 to678 of FIG. 113 (SEQ ID NO:179).

In yet another aspect, the invention concerns an isolated PRO1277polypeptide, comprising the sequence of amino acid residues 27 to about678, inclusive of FIG. 113 (SEQ ID NO:179), or a fragment thereofsufficient to provide a binding site for an anti-PRO1277 antibody.Preferably, the PRO1277 fragment retains a qualitative biologicalactivity of a native PRO1277 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1277 polypeptide having the sequence ofamino acid residues from about 27 to about 678, inclusive of FIG. 113(SEQ ID NO:179), or (b) the complement of the DNA molecule of (a), andif the test DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1277 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1277 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1277 polypeptide, by contactingthe native PRO1277 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1277 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

45. PRO1135

Applicants have identified a cDNA clone that encodes a novel polypeptidehaving homology to alpha 1,2-mannosidase, wherein the polypeptide isdesignated in the present application as “PRO1135”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1135 polypeptide. In one aspect,the isolated nucleic acid comprises DNA encoding the PRO1135 polypeptidehaving amino acid residues 1 to 541 of FIG. 115 (SEQ ID NO:181), or iscomplementary to such encoding nucleic acid sequence, and remains stablybound to it under at least moderate, and optionally, under highstringency conditions. In other aspects, the isolated nucleic acidcomprises DNA encoding the PRO1135 polypeptide having amino acidresidues about 22 to 541 of FIG. 115 (SEQ ID NO:181), or iscomplementary to such encoding nucleic acid sequence, and remains stablybound to it under at least moderate, and optionally, under highstringency conditions. The isolated nucleic acid sequence may comprisethe cDNA insert of the DNA56870-1492 vector deposited on Jun. 2, 1998 asATCC 209925 which includes the nucleotide sequence encoding PRO1135.

In another embodiment, the invention provides isolated PRO1135polypeptide. In particular, the invention provides isolated nativesequence PRO1135 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 to 541 of FIG. 115 (SEQ ID NO:181).Additional embodiments of the present invention are directed to PRO1135polypeptides comprising amino acids about 22 to 541 of FIG. 115 (SEQ IDNO:181). Optionally, the PRO1135 polypeptide is obtained or isobtainable by expressing the polypeptide encoded by the cDNA insert ofthe DNA56870-1492 vector deposited on Jun. 2, 1998 as ATCC 209925.

46. PRO1114

A cDNA clone (DNA57033-1403) has been identified that encodes a novelinterferon receptor polypeptide, designated in the present applicationas “PRO1114 interferon receptor”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1114 interferon receptorpolypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1114 interferon receptor polypeptide having the sequenceof amino acid residues from about 1 or about 30 to about 311, inclusiveof FIG. 117 (SEQ ID NO:183), or (b) the complement of the DNA moleculeof (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1114 interferon receptor polypeptide comprisingDNA hybridizing to the complement of the nucleic acid between aboutnucleotides 250 or about 337 and about 1182, inclusive, of FIG. 116 (SEQID NO:182). Preferably, hybridization occurs under stringenthybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 209905(DNA57033-1403) or (b) the complement of the nucleic acid molecule of(a). In a preferred embodiment, the nucleic acid comprises a DNAencoding the same mature polypeptide encoded by the human protein cDNAin ATCC Deposit No. 209905 (DNA57033-1403).

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 30 to about 311, inclusive of FIG. 117 (SEQ IDNO:183), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least 10 nucleotides and produced by hybridizing atest DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1114 interferon receptor polypeptide having the sequenceof amino acid residues from 1 or about 30 to about 311, inclusive ofFIG. 117 (SEQ ID NO:183), or (b) the complement of the DNA molecule of(a), and, if the DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), isolating the testDNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1114 interferon receptorpolypeptide, with or without the N-terminal signal sequence and/or theinitiating methionine, and its soluble, i.e., transmembrane domaindeleted or inactivated variants, or is complementary to such encodingnucleic acid molecule. The signal peptide has been tentativelyidentified as extending from about amino acid position 1 to about aminoacid position 29 in the sequence of FIG. 117 (SEQ ID NO:183). Thetransmembrane domain has been tentatively identified as extending fromabout amino acid position 230 to about amino acid position 255 in thePRO1114 interferon receptor amino acid sequence (FIG. 117, SEQ IDNO:183).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 30 to about 311, inclusive of FIG. 117 (SEQ ID NO:183), or (b)the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1114 interferonreceptor polypeptide coding sequence that may find use as hybridizationprobes. Such nucleic acid fragments are from about 20 to about 80nucleotides in length, preferably from about 20 to about 60 nucleotidesin length, more preferably from about 20 to about 50 nucleotides inlength and most preferably from about 20 to about 40 nucleotides inlength and may be derived from the nucleotide sequence shown in FIG. 116(SEQ ID NO:182).

In another embodiment, the invention provides isolated PRO1114interferon receptor polypeptide encoded by any of the isolated nucleicacid sequences hereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO1114 interferon receptor polypeptide, which in certain embodiments,includes an amino acid sequence comprising residues 1 or about 30 toabout 311 of FIG. 117 (SEQ ID NO:183).

In another aspect, the invention concerns an isolated PRO1114 interferonreceptor polypeptide, comprising an amino acid sequence having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 30 to about 311, inclusive of FIG. 117 (SEQ IDNO:183).

In a further aspect, the invention concerns an isolated PRO1114interferon receptor polypeptide, comprising an amino acid sequencescoring at least about 80% positives, preferably at least about 85%positives, more preferably at least about 90% positives, most preferablyat least about 95% positives when compared with the amino acid sequenceof residues 1 or about 30 to about 311, inclusive of FIG. 117 (SEQ IDNO:183).

In yet another aspect, the invention concerns an isolated PRO1114interferon receptor polypeptide, comprising the sequence of amino acidresidues 1 or about 30 to about 311, inclusive of FIG. 117 (SEQ IDNO:183), or a fragment thereof sufficient to provide a binding site foran anti-PRO1114 interferon receptor antibody. Preferably, the PRO1114interferon receptor fragment retains a qualitative biological activityof a native PRO1114 interferon receptor polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1114 interferon receptor polypeptidehaving the sequence of amino acid residues from about 1 or about 30 toabout 311, inclusive of FIG. 117 (SEQ ID NO:183), or (b) the complementof the DNA molecule of (a), and if the test DNA molecule has at leastabout an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), (ii) culturing a host cell comprising the test DNA moleculeunder conditions suitable for expression of the polypeptide, and (iii)recovering the polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1114 interferon receptor polypeptide. In aparticular embodiment, the agonist or antagonist is an anti-PRO1114interferon receptor antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1114 interferon receptorpolypeptide by contacting the native PRO1114 interferon receptorpolypeptide with a candidate molecule and monitoring a biologicalactivity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1114 interferon receptor polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

In another embodiment, the invention provides an expressed sequence tag(EST) designated herein as DNA48466 comprising the nucleotide sequenceof SEQ ID NO:184 (see FIG. 118).

47. PRO828

Applicants have identified a cDNA clone that encodes a novel polypeptidehaving homology to glutathione peroxidases wherein the polypeptide isdesignated in the present application as “PRO828”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO828 polypeptide. In one aspect,the isolated nucleic acid comprises DNA encoding the PRO828 polypeptidehaving amino acid residues 1 to 187 of FIG. 120 (SEQ ID NO:189), or iscomplementary to such encoding nucleic acid sequence, and remains stablybound to it under at least moderate, and optionally, under highstringency conditions. In other aspects, the isolated nucleic acidcomprises DNA encoding the PRO828 polypeptide having amino acid residuesabout 22 to 187 of FIG. 120 (SEQ ID NO:189), or is complementary to suchencoding nucleic acid sequence, and remains stably bound to it under atleast moderate, and optionally, under high stringency conditions. Theisolated nucleic acid sequence may comprise the cDNA insert of theDNA57037-1444 vector deposited on May 27, 1998 as ATCC 209903 whichincludes the nucleotide sequence encoding PRO828.

In another embodiment, the invention provides isolated PRO828polypeptide. In particular, the invention provides isolated nativesequence PRO828 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 to 187 of FIG. 120 (SEQ ID NO:189).Additional embodiments of the present invention are directed to PRO828polypeptides comprising amino acids about 22 to 187 of FIG. 120 (SEQ IDNO:189). Optionally, the PRO828 polypeptide is obtained or is obtainableby expressing the polypeptide encoded by the cDNA insert of theDNA57037-1444 vector deposited on May 27, 1998 as ATCC 209903.

48. PRO1009

A cDNA clone (DNA57129-1413) has been identified, having sequenceidentity with a long chain acyl-CoA synthetase homologue, a long chainacyl-CoA synthetase and a long chain acyl-CoA synthetase ligase thatencodes a novel polypeptide, designated in the present application as“PRO1009.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1009 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1009 polypeptide having the sequence of amino acidresidues from about 1 or 23 to about 615, inclusive of FIG. 122 (SEQ IDNO:194), or (b) the complement of the DNA molecule of (a). The term “or”as used herein to refer to amino or nucleic acids is meant to refer totwo separate alternative embodiments provided herein, i.e., 1–615 or23–615.

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1009 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 41 or 107 andabout 1885, inclusive, of FIG. 121 (SEQ ID NO:193). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 209977(DNA57129-1413), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.209977 (DNA57129-1413).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 1 or 23 to about 615, inclusive of FIG. 122(SEQ ID NO:194), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule produced by hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1009 polypeptide havingthe sequence of amino acid residues from about 1 or 23 to about 615,inclusive of FIG. 122 (SEQ ID NO:194), or (b) the complement of the DNAmolecule of (a), and, if the DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), isolating the testDNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1009 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, and itssoluble, i.e. transmembrane domain deleted or inactivated variants, oris complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from amino acidposition 1 to about amino acid position 22 in the sequence of FIG. 122(SEQ ID NO:194). The transmembrane domains have been tentativelyidentified as extending from about amino acid positions 140–161, 213–229and 312–334 in the PRO1009 amino acid sequence (FIG. 122, SEQ IDNO:194).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 23 to about 615, inclusive of FIG. 122 (SEQ ID NO:194), or (b) thecomplement of the DNA of (a).

In another embodiment, the invention provides isolated PRO1009polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1009 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 or 23 to 615 of FIG. 122 (SEQ ID NO:194).

In another aspect, the invention concerns an isolated PRO1009polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 23 to about 615, inclusive of FIG. 122 (SEQ ID NO:194).

In a further aspect, the invention concerns an isolated PRO1009polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 23to 615 of FIG. 122 (SEQ ID NO:194).

In yet another aspect, the invention concerns an isolated PRO1009polypeptide, comprising the sequence of amino acid residues 1 or 23 toabout 615, inclusive of FIG. 122 (SEQ ID NO:194), or a fragment thereofsufficient to provide a binding site for an anti-PRO1009 antibody.Preferably, the PRO1009 fragment retains a qualitative biologicalactivity of a native PRO1009 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1009 polypeptide having the sequence ofamino acid residues from about 1 or 23 through about 615, inclusive ofFIG. 122 (SEQ ID NO:194), or (b) the complement of the DNA molecule of(a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1009 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1009 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1009 polypeptide, by contactingthe native PRO1009 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1009 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

In another embodiment, the invention provides an expressed sequence tag(EST) designated herein as DNA50853 comprising the nucleotide sequenceof FIG. 123 (SEQ ID NO:195).

49. PRO1007

Applicants have identified a cDNA clone that encodes a novel polypeptidehaving sequence identity with MAGPIAP, wherein the polypeptide isdesignated in the present application as “PRO1007”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1007 polypeptide. In one aspect,the isolated nucleic acid comprises DNA encoding the PRO1007 polypeptidehaving amino acid residues 1 through 346 of FIG. 125 (SEQ ID NO:197), oris complementary to such encoding nucleic acid sequence, and remainsstably bound to it under at least moderate, and optionally, under highstringency conditions. The isolated nucleic acid sequence may comprisethe cDNA insert of the vector deposited on Jun. 9, 1998 with the ATCC asDNA57690-1374 which includes the nucleotide sequence encoding PRO1007.

In another embodiment, the invention provides isolated PRO1007polypeptide. In particular, the invention provides isolated nativesequence PRO1007 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 through 346 of FIG. 125 (SEQ IDNO:197). An additional embodiment of the present invention is directedto an isolated extracellular domain of a PRO1007 polypeptide.Optionally, the PRO1007 polypeptide is obtained or is obtainable byexpressing the polypeptide encoded by the cDNA insert of the vectordeposited with the ATCC on Jun. 9, 1998 as DNA57690-1374.

50. PRO1056

A cDNA clone (DNA57693-1424) has been identified, having homology tonucleic acid encoding a chloride channel protein that encodes a novelpolypeptide, designated in the present application as “PRO1056”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1056 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1056 polypeptide having the sequence of amino acidresidues from about 1 or about 19 to about 120, inclusive of FIG. 127(SEQ ID NO:199), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1056 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about nucleotides 56 or about110 and about 415, inclusive, of FIG. 126 (SEQ ID NO:198). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203008(DNA57693-1424) or (b) the complement of the nucleic acid molecule of(a). In a preferred embodiment, the nucleic acid comprises a DNAencoding the same mature polypeptide encoded by the human protein cDNAin ATCC Deposit No. 203008 (DNA57693-1424).

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 19 to about 120, inclusive of FIG. 127 (SEQ IDNO:199), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least 10 nucleotides and produced by hybridizing atest DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1056 polypeptide having the sequence of amino acidresidues from 1 or about 19 to about 120, inclusive of FIG. 127 (SEQ IDNO:199), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, preferably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1056 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, and itssoluble, i.e., transmembrane domain deleted or inactivated variants, oris complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from about aminoacid position 1 to about amino acid position 18 in the sequence of FIG.127 (SEQ ID NO:199). The transmembrane domain has been tentativelyidentified as extending from about amino acid position 39 to about aminoacid position 58 in the PRO1056 amino acid sequence (FIG. 127, SEQ IDNO:199).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 19 to about 120, inclusive of FIG. 127 (SEQ ID NO:199), or (b)the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1056 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 126 (SEQ ID NO:198).

In another embodiment, the invention provides isolated PRO1056polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO1056 polypeptide, which in certain embodiments, includes an aminoacid sequence comprising residues 1 or about 19 to about 120 of FIG. 127(SEQ ID NO:199).

In another aspect, the invention concerns an isolated PRO1056polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 19 to about 120, inclusive of FIG. 127 (SEQ ID NO:199).

In a further aspect, the invention concerns an isolated PRO1056polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 19 to about 120, inclusive of FIG. 127 (SEQ ID NO:199).

In yet another aspect, the invention concerns an isolated PRO1056polypeptide, comprising the sequence of amino acid residues 1 or about19 to about 120, inclusive of FIG. 127 (SEQ ID NO:199), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1056antibody. Preferably, the PRO1056 fragment retains a qualitativebiological activity of a native PRO1056 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1056 polypeptide having the sequence ofamino acid residues from about 1 or about 19 to about 120, inclusive ofFIG. 127 (SEQ ID NO:199), or (b) the complement of the DNA molecule of(a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1056 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1056 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1056 polypeptide by contactingthe native PRO1056 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1056 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

51. PRO826

A cDNA clone (DNA57694-1341) has been identified that encodes a novelsecreted polypeptide, designated in the present application as “PRO826”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO826 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO826 polypeptide having the sequence of amino acid residuesfrom about 1 or about 23 to about 99, inclusive of FIG. 129 (SEQ IDNO:201), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO826 polypeptide comprising DNA hybridizing to thecomplement of the nucleic acid between about nucleotides 13 or about 79and about 309, inclusive, of FIG. 128 (SEQ ID NO:200). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203017(DNA57694-1341) or (b) the complement of the nucleic acid molecule of(a). In a preferred embodiment, the nucleic acid comprises a DNAencoding the same mature polypeptide encoded by the human protein cDNAin ATCC Deposit No. 203017 (DNA57694-1341).

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 23 to about 99, inclusive of FIG. 129 (SEQ IDNO:201), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least 10 nucleotides and produced by hybridizing atest DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO826 polypeptide having the sequence of amino acid residuesfrom 1 or about 23 to about 99, inclusive of FIG. 129 (SEQ ID NO:201),or (b) the complement of the DNA molecule of (a), and, if the DNAmolecule has at least about an 80% sequence identity, preferably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO826 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, or iscomplementary to such encoding nucleic acid molecule. The signal peptidehas been tentatively identified as extending from about amino acidposition 1 to about amino acid position 22 in the sequence of FIG. 129(SEQ ID NO:201).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 23 to about 99, inclusive of FIG. 129 (SEQ ID NO:201), or (b)the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO826 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 128 (SEQ ID NO:200).

In another embodiment, the invention provides isolated PRO826polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO826 polypeptide, which in certain embodiments, includes an amino acidsequence comprising residues 1 or about 23 to about 99 of FIG. 129 (SEQID NO:201).

In another aspect, the invention concerns an isolated PRO826polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 23 to about 99, inclusive of FIG. 129 (SEQ ID NO:201).

In a further aspect, the invention concerns an isolated PRO826polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 23 to about 99, inclusive of FIG. 129 (SEQ ID NO:201).

In yet another aspect, the invention concerns an isolated PRO826polypeptide, comprising the sequence of amino acid residues 1 or about23 to about 99, inclusive of FIG. 129 (SEQ ID NO:201), or a fragmentthereof sufficient to provide a binding site for an anti-PRO826antibody. Preferably, the PRO826 fragment retains a qualitativebiological activity of a native PRO826 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO826 polypeptide having the sequence ofamino acid residues from about 1 or about 23 to about 99, inclusive ofFIG. 129 (SEQ ID NO:201), or (b) the complement of the DNA molecule of(a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

52. PRO819

A cDNA clone (DNA57695-1340) has been identified that encodes a novelsecreted polypeptide, designated in the present application as “PRO819”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO819 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO819 polypeptide having the sequence of amino acid residuesfrom about 1 or about 25 to about 52, inclusive of FIG. 131 (SEQ IDNO:203), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO819 polypeptide comprising DNA hybridizing to thecomplement of the nucleic acid between about nucleotides 46 or about 118and about 201, inclusive, of FIG. 130 (SEQ ID NO:202). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203006(DNA57695-1340) or (b) the complement of the nucleic acid molecule of(a). In a preferred embodiment, the nucleic acid comprises a DNAencoding the same mature polypeptide encoded by the human protein cDNAin ATCC Deposit No. 203006 (DNA57695-1340).

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 25 to about 52, inclusive of FIG. 131 (SEQ IDNO:203), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least 10 nucleotides and produced by hybridizing atest DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO819 polypeptide having the sequence of amino acid residuesfrom 1 or about 25 to about 52, inclusive of FIG. 131 (SEQ ID NO:203),or (b) the complement of the DNA molecule of (a), and, if the DNAmolecule has at least about an 80% sequence identity, preferably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO819 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, or iscomplementary to such encoding nucleic acid molecule. The signal peptidehas been tentatively identified as extending from about amino acidposition 1 to about amino acid position 24 in the sequence of FIG. 131(SEQ ID NO:203).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 25 to about 52, inclusive of FIG. 131 (SEQ ID NO:203), or (b)the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO819 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 130 (SEQ ID NO:202).

In another embodiment, the invention provides isolated PRO819polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO819 polypeptide, which in certain embodiments, includes an amino acidsequence comprising residues 1 or about 25 to about 52 of FIG. 131 (SEQID NO:203).

In another aspect, the invention concerns an isolated PRO819polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 25 to about 52, inclusive of FIG. 131 (SEQ ID NO:203).

In a further aspect, the invention concerns an isolated PRO819polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 25 to about 52, inclusive of FIG. 131 (SEQ ID NO:203).

In yet another aspect, the invention concerns an isolated PRO819polypeptide, comprising the sequence of amino acid residues 1 or about25 to about 52, inclusive of FIG. 131 (SEQ ID NO:203), or a fragmentthereof sufficient to provide a binding site for an anti-PRO819antibody. Preferably, the PRO819 fragment retains a qualitativebiological activity of a native PRO819 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO819 polypeptide having the sequence ofamino acid residues from about 1 or about 25 to about 52, inclusive ofFIG. 131 (SEQ ID NO:203), or (b) the complement of the DNA molecule of(a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

53. PRO1006

A cDNA clone (DNA57699-1412) has been identified, having sequenceidentity with a virud protein believed to be a tyrosine protein kinase,that encodes a novel polypeptide, designated in the present applicationas “PRO1006.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1006 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1006 polypeptide having the sequence of amino acidresidues from about 1 or 24 to about 392, inclusive of FIG. 133 (SEQ IDNO:205), or (b) the complement of the DNA molecule of (a). The term “or”as used herein to refer to amino or nucleic acids is meant to refer totwo alternative embodiments provided herein, i.e., 1–392, or in anotherembodiment, 24–392.

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1006 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 28 or 97 andabout 1203, inclusive, of FIG. 132 (SEQ ID NO:204). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203020(DNA57699-1412), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203020 (DNA57699-1412).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 1 or 24 to about 392, inclusive of FIG. 133(SEQ ID NO:205), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule produced by hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1006 polypeptide havingthe sequence of amino acid residues from about 1 or 24 to about 392,inclusive of FIG. 133 (SEQ ID NO:205), or (b) the complement of the DNAmolecule of (a), and, if the DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), isolating the testDNA molecule.

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 24 to about 392, inclusive of FIG. 133 (SEQ ID NO:205), or (b) thecomplement of the DNA of (a).

In another embodiment, the invention provides isolated PRO1006polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1006 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 or 24 through 392 of FIG. 133 (SEQ IDNO:205).

In another aspect, the invention concerns an isolated PRO1006polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 24 to about 392, inclusive of FIG. 133 (SEQ ID NO:205).

In a further aspect, the invention concerns an isolated PRO1006polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 24through 392 of FIG. 133 (SEQ ID NO:205).

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1006 polypeptide having the sequence ofamino acid residues from about 1 or 24 to about 392, inclusive of FIG.133 (SEQ ID NO:205), or (b) the complement of the DNA molecule of (a),and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1006 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1006 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1006 polypeptide, by contactingthe native PRO1006 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1006 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

54. PRO1112

Applicants have identified a cDNA clone that encodes a novel polypeptidehaving multiple transmembrane domains and having some sequence identitywith a Mycobacterium tuberculosis peptide, a peptide found in a Dayhoffdatabase designated as “MTY20B11_(—)13”, wherein the novel polypeptideis designated in the present application as “PRO1112”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1112 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1112 polypeptide having the sequence of amino acidresidues from 1 or about 14 through about 262 of FIG. 135 (SEQ IDNO:207), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1112 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues about 20 or 59through 809 of FIG. 134 (SEQ ID NO:206). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in the ATCC Deposit ofDNA57702-1476 made on Jun. 9, 1998. In a preferred embodiment, thenucleic acid comprises a DNA encoding the same mature polypeptideencoded by the human protein cDNA in the ATCC Deposit of DNA57702-1476made on Jun. 9, 1998.

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 14 through about 262 of FIG. 135 (SEQ IDNO:207).

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1112 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, and itssoluble, i.e., transmembrane domains deleted or inactivated variants, oris complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from amino acidposition 1 through about amino acid position 13 of FIG. 135 (SEQ IDNO:207). The transmembrane domains have been tentatively identified asextending from about amino acid positions 58–76, 99–113, 141–159 and203–222 of FIG. 135 (SEQ ID NO:207).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA encoding a polypeptide scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 14 through 262 of FIG. 135 (SEQ ID NO:207).

Another embodiment is directed to fragments of a PRO1112 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 60 to about 100 nucleotides in length.

In another embodiment, the invention provides isolated PRO1112polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO1112 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 or 14 through about 262 of FIG. 135 (SEQID NO:207).

In another aspect, the invention concerns an isolated PRO1112polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 14 through about 262 of FIG. 135 (SEQ ID NO:207).

In a further aspect, the invention concerns an isolated PRO1112polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 14 through about 262 of FIG. 135 (SEQ ID NO:207).

In yet another aspect, the invention concerns an isolated PRO1112polypeptide, comprising the sequence of amino acid residues 1 or about14 through about 262 of FIG. 135 (SEQ ID NO:207), or a fragment thereofsufficient to provide a binding site for an anti-PRO1112 antibody.Preferably, the PRO1112 fragment retains a qualitative biologicalactivity of a native PRO1112 polypeptide.

In another aspect, the present invention is directed to fragments of aPRO1112 polypeptide which are sufficiently long to provide an epitopeagainst which an antibody may be generated.

55. PRO1074

Applicants have identified a cDNA clone, DNA57704-1452, that encodes anovel polypeptide having homology to galactosyltransferase, wherein thepolypeptide is designated in the present application as “PRO1074”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1074 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, and mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1074 polypeptide having the sequence of amino acidresidues from 1 to about 331, inclusive of FIG. 137 (SEQ ID NO:209), or(b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1074 polypeptide comprising DNA that hybridizesto the complement of the nucleic acid sequence having about residues 322to 1314, inclusive of FIG. 136 (SEQ ID NO:208). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, and most preferably at least about95% sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 209953(DNA57704-1452), which was deposited on Jun. 9, 1998, or (b) thecomplement of the DNA molecule of (a). In a preferred embodiment, thenucleic acid comprises a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 209953(DNA57704-1452).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, and mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 to about 331, inclusive of FIG. 137 (SEQ ID NO:209).

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1074 extracellular domain (ECD),with or without the initiating methionine, and its soluble variants(i.e. transmembrane domain(s) deleted or inactivated) or iscomplementary to such encoding nucleic acid molecule. A type IItransmembrane domain region has been tentatively identified as extendingfrom about amino acid position 20 to 39 in the PRO1074 amino acidsequence (FIG. 137, SEQ ID NO:209).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA encoding a polypeptide scoring at least about80% positives, preferably at least about 90% positives, and mostpreferably at least about 95% positives when compared with the aminoacid sequence of residues 1 to about 331, inclusive of FIG. 137 (SEQ IDNO:209).

Another embodiment is directed to fragments of a PRO1074 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1074polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO1074 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 to 331 of FIG. 137 (SEQ ID NO:209).

In another aspect, the invention concerns an isolated PRO1074polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, and most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 to 331, inclusive of FIG. 137 (SEQ ID NO:209).

In a further aspect, the invention concerns an isolated PRO1074polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, and most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 toabout 331 of FIG. 137 (SEQ ID NO:209).

In another aspect, the invention concerns a PRO1074 extracellular domaincomprising an amino acid sequence having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, and most preferably atleast about 95% sequence identity to the sequence of amino acid residuesX to 331 of FIG. 2 (SEQ ID NO:3), wherein X is any one of amino acidresidues 35 to 44 of FIG. 137 (SEQ ID NO:209).

In yet another aspect, the invention concerns an isolated PRO1074polypeptide, comprising the sequence of amino acid residues 1 to about331, inclusive of FIG. 137 (SEQ ID NO:209), or a fragment thereofsufficient to provide a binding site for an anti-PRO1074 antibody.Preferably, the PRO1074 fragment retains a qualitative biologicalactivity of a native PRO1074 polypeptide.

In another aspect, the present invention is directed to fragments of aPRO1074 polypeptide which are sufficiently long to provide an epitopeagainst which an antibody may be generated.

In yet another embodiment, the invention concerns agonist andantagonists of the PRO1074 polypeptide. In a particular embodiment, theagonist or antagonist is an anti-PRO1074 antibody.

In a further embodiment, the invention concerns screening assays toidentify agonists or antagonists of a native PRO1074 polypeptide.

In still a further embodiment, the invention concerns a compositioncomprising a PRO1074 polypeptide as hereinabove defined, in combinationwith a pharmaceutically acceptable carrier.

56. PRO1005

A cDNA clone (DNA57708-1411) has been identified that encodes a novelpolypeptide, designated in the present application as “PRO1005.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1005 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1005 polypeptide having the sequence of amino acidresidues from about 21 to about 185, inclusive of FIG. 139 (SEQ IDNO:211), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1005 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 90 and about584, inclusive, of FIG. 138 (SEQ ID NO:210). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203021(DNA57708-1411), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203021 (DNA57708-1411).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 21 to about 185, inclusive of FIG. 139 (SEQ IDNO:211), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least 50 nucleotides, and preferably at least 100nucleotides, and produced by hybridizing a test DNA molecule understringent conditions with (a) a DNA molecule encoding a PRO1005polypeptide having the sequence of amino acid residues from about 21 toabout 185, inclusive of FIG. 139 (SEQ ID NO:211), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least aboutan 80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1005 polypeptide, with or withoutthe N-terminal signal sequence, or is complementary to such encodingnucleic acid molecule. The signal peptide has been tentativelyidentified as extending from amino acid position 1 through about aminoacid position 20 in the sequence of FIG. 139 (SEQ ID NO:211).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 21to about 185, inclusive of FIG. 139 (SEQ ID NO:211), or (b) thecomplement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1005 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1005polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1005 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 21 to 185 of FIG. 139 (SEQ ID NO:211).

In another aspect, the invention concerns an isolated PRO1005polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues21 to about 185, inclusive of FIG. 139 (SEQ ID NO:211).

In a further aspect, the invention concerns an isolated PRO1005polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 21 to185 of FIG. 139 (SEQ ID NO:211).

In yet another aspect, the invention concerns an isolated PRO1005polypeptide, comprising the sequence of amino acid residues 21 to about185, inclusive of FIG. 139 (SEQ ID NO:211), or a fragment thereofsufficient to provide a binding site for an anti-PRO1005 antibody.Preferably, the PRO1005 fragment retains a qualitative biologicalactivity of a native PRO1005 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1005 polypeptide having the sequence ofamino acid residues from about 21 to about 185, inclusive of FIG. 139(SEQ ID NO:211), or (b) the complement of the DNA molecule of (a), andif the test DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

57. PRO1073

A cDNA clone (DNA57710-1451) has been identified that encodes a novelpolypeptide, designated in the present application as “PRO1073.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1073 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1073 polypeptide having the sequence of amino acidresidues from about 32 to about 299, inclusive of FIG. 141 (SEQ IDNO:213), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1073 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 438 and about1241, inclusive, of FIG. 140 (SEQ ID NO:212). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203048(DNA57710-1451), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203048 (DNA57710-1451).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 32 to about 299, inclusive of FIG. 141 (SEQ IDNO:213), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least about 50 nucleotides, and preferably at leastabout 100 nucleotides and produced by hybridizing a test DNA moleculeunder stringent conditions with (a) a DNA molecule encoding a PRO1073polypeptide having the sequence of amino acid residues from about 32 toabout 299, inclusive of FIG. 141 (SEQ ID NO:213), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least aboutan 80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1073 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, or iscomplementary to such encoding nucleic acid molecule. The signal peptidehas been tentatively identified as extending from amino acid position 1through about amino acid position 31 in the sequence of FIG. 141 (SEQ IDNO:213).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 32to about 299, inclusive of FIG. 141 (SEQ ID NO:213), or (b) thecomplement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1073 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1073polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1073 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 32 to 299 of FIG. 141 (SEQ ID NO:213).

In another aspect, the invention concerns an isolated PRO1073polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues32 to about 299, inclusive of FIG. 141 (SEQ ID NO:213).

In a further aspect, the invention concerns an isolated PRO1073polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 32 to299 of FIG. 141 (SEQ ID NO:213).

In yet another aspect, the invention concerns an isolated PRO1073polypeptide, comprising the sequence of amino acid residues 32 to about299, inclusive of FIG. 141 (SEQ ID NO:213), or a fragment thereofsufficient to provide a binding site for an anti-PRO1073 antibody.Preferably, the PRO1073 fragment retains a qualitative biologicalactivity of a native PRO1073 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1073 polypeptide having the sequence ofamino acid residues from about 32 to about 299, inclusive of FIG. 141(SEQ ID NO:213), or (b) the complement of the DNA molecule of (a), andif the test DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

58. PRO1152

A cDNA clone (DNA57711-1501) has been identified that encodes a noveltransmembrane polypeptide, designated in the present application as“PRO1152”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO152 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1152 polypeptide having the sequence of amino acidresidues from about 1 or about 29 to about 479, inclusive of FIG. 144(SEQ ID NO:216), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1152 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about nucleotides 58 or about142 and about 1494, inclusive, of FIG. 143 (SEQ ID NO:215). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203047(DNA57711-1501) or (b) the complement of the nucleic acid molecule of(a). In a preferred embodiment, the nucleic acid comprises a DNAencoding the same mature polypeptide encoded by the human protein cDNAin ATCC Deposit No. 203047 (DNA57711-1501).

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 29 to about 479, inclusive of FIG. 144 (SEQ IDNO:216), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least 300 nucleotides and produced by hybridizing atest DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1152 polypeptide having the sequence of amino acidresidues from 1 or about 29 to about 479, inclusive of FIG. 144 (SEQ IDNO:216), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, preferably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1152 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, and itssoluble, i.e., transmembrane domain deleted or inactivated variants, oris complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from about aminoacid position 1 to about amino acid position 28 in the sequence of FIG.144 (SEQ ID NO:216). The various transmembrane domains have beententatively identified as extending from about amino acid position 133to about amino acid position 155, from about amino acid position 168 toabout amino acid position 187, from about amino acid position 229 toabout amino acid position 247, from about amino acid position 264 toabout amino acid position 285, from about amino acid position 309 toabout amino acid position 330, from about amino acid position 371 toabout amino acid position 390 and from about amino acid position 441 toabout amino acid position 464 in the PRO1152 amino acid sequence (FIG.144, SEQ ID NO:216).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 29 to about 479, inclusive of FIG. 144 (SEQ ID NO:216), or (b)the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1152 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 143 (SEQ ID NO:215).

In another embodiment, the invention provides isolated PRO1152polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO1152 polypeptide, which in certain embodiments, includes an aminoacid sequence comprising residues 1 or about 29 to about 479 of FIG. 144(SEQ ID NO:216).

In another aspect, the invention concerns an isolated PRO1152polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 29 to about 479, inclusive of FIG. 144 (SEQ ID NO:216).

In a further aspect, the invention concerns an isolated PRO1152polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 29 to about 479, inclusive of FIG. 144 (SEQ ID NO:216).

In yet another aspect, the invention concerns an isolated PRO1152polypeptide, comprising the sequence of amino acid residues 1 or about29 to about 479, inclusive of FIG. 144 (SEQ ID NO:216), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1152antibody. Preferably, the PRO1152 fragment retains a qualitativebiological activity of a native PRO1152 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1152 polypeptide having the sequence ofamino acid residues from about 1 or about 29 to about 479, inclusive ofFIG. 144 (SEQ ID NO:216), or (b) the complement of the DNA molecule of(a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In another embodiment, the invention provides a nucleic aid moleculedesignated herein as DNA55807 comprising the nucleotide sequence of SEQID NO:217 (see FIG. 145).

59. PRO1136

A cDNA clone (DNA57827-1493) has been identified, having homology tonucleic acid encoding PDZ domain-containing proteins that encodes anovel polypeptide, designated in the present application as “PRO1136”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1136 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1136 polypeptide having the sequence of amino acidresidues from about 1 or about 16 to about 632, inclusive of FIG. 147(SEQ ID NO:219), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1136 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about nucleotides 216 orabout 261 and about 2111, inclusive, of FIG. 146 (SEQ ID NO:218).Preferably, hybridization occurs under stringent hybridization and washconditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203045(DNA57827-1493) or (b) the complement of the nucleic acid molecule of(a). In a preferred embodiment, the nucleic acid comprises a DNAencoding the same mature polypeptide encoded by the human protein cDNAin ATCC Deposit No. 203045 (DNA57827-1493).

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 16 to about 632, inclusive of FIG. 147 (SEQ IDNO:219), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least 10 nucleotides and produced by hybridizing atest DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1136 polypeptide having the sequence of amino acidresidues from 1 or about 16 to about 632, inclusive of FIG. 147 (SEQ IDNO:219), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, preferably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1136 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, or iscomplementary to such encoding nucleic acid molecule. The signal peptidehas been tentatively identified as extending from about amino acidposition 1 to about amino acid position 15 in the sequence of FIG. 147(SEQ ID NO:219).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 16 to about 632, inclusive of FIG. 147 (SEQ ID NO:219), or (b)the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1136 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 146 (SEQ ID NO:218).

In another embodiment, the invention provides isolated PRO1136polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO1136 polypeptide, which in certain embodiments, includes an aminoacid sequence comprising residues 1 or about 16 to about 632 of FIG. 147(SEQ ID NO:219).

In another aspect, the invention concerns an isolated PRO1136polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 16 to about 632, inclusive of FIG. 147 (SEQ ID NO:219).

In a further aspect, the invention concerns an isolated PRO1136polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 16 to about 632, inclusive of FIG. 147 (SEQ ID NO:219).

In yet another aspect, the invention concerns an isolated PRO1136polypeptide, comprising the sequence of amino acid residues 1 or about16 to about 632, inclusive of FIG. 147 (SEQ ID NO:219), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1136antibody. Preferably, the PRO1136 fragment retains a qualitativebiological activity of a native PRO1136 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1136 polypeptide having the sequence ofamino acid residues from about 1 or about 16 to about 632, inclusive ofFIG. 147 (SEQ ID NO:219), or (b) the complement of the DNA molecule of(a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1136 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1136 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1136 polypeptide by contactingthe native PRO1136 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1136 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

60. PRO813

Applicants have identified a cDNA clone (DNA57834-1339) having homologyto pulmonary surfactant-associated protein C that encodes a novelpolypeptide, designated in the present application as “PRO813”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO813 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO813 polypeptide having the sequence of amino acid residuesfrom about 1 or about 27 to about 176, inclusive of FIG. 149 (SEQ IDNO:221), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO813 polypeptide comprising DNA hybridizing to thecomplement of the nucleic acid between about nucleotides 109 or about187 and about 636, inclusive, of FIG. 148 (SEQ ID NO:220). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 209954(DNA57834-1339). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 209954 (DNA57834-1339).

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 27 to about 176, inclusive of FIG. 149 (SEQ IDNO:221).

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO813 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, or iscomplementary to such encoding nucleic acid molecule. The signal peptidehas been tentatively identified as extending from about amino acidposition 1 to about amino acid position 26 in the sequence of FIG. 149(SEQ ID NO:221).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA encoding a polypeptide scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 27 to about 176, inclusive of FIG. 149 (SEQ ID NO:221).

Another embodiment is directed to fragments of a PRO813 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO813polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO813 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 or about 27 to about 176 of FIG. 149 (SEQID NO:221).

In another aspect, the invention concerns an isolated PRO813polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 27 to about 176, inclusive of FIG. 149 (SEQ ID NO:221).

In a further aspect, the invention concerns an isolated PRO813polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 27 to about 176, inclusive of FIG. 149 (SEQ ID NO:221).

In yet another aspect, the invention concerns an isolated PRO813polypeptide, comprising the sequence of amino acid residues 1 or about27 to about 176, inclusive of FIG. 149 (SEQ ID NO:221), or a fragmentthereof sufficient to provide a binding site for an anti-PRO813antibody. Preferably, the PRO813 fragment retains a qualitativebiological activity of a native PRO813 polypeptide.

In another aspect, the present invention is directed to fragments of aPRO813 polypeptide which are sufficiently long to provide an epitopeagainst which an antibody may be generated.

In yet another embodiment, the invention concerns agonists andantagonists of a native PRO813 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO813 antibody.

In a further embodiment, the invention concerns screening assays toidentify agonists or antagonists of a native PRO813 polypeptide.

In still a further embodiment, the invention concerns a compositioncomprising a PRO813 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

61. PRO809

A cDNA clone (DNA57836-1338) has been identified, having sequenceidentity with heparan sulfate proteoglycans, that encodes a novelpolypeptide, designated in the present application as “PRO809.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO809 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO809 polypeptide having the sequence of amino acid residuesfrom about 1 or 19 to about 265, inclusive of FIG. 151 (SEQ ID NO:223),or (b) the complement of the DNA molecule of (a). The term “or” as usedherein to refer to amino or nucleic acids is meant to refer to twoalternative embodiments provided herein, i.e., 1-265, or in anotherembodiment, 19–265.

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO809 polypeptide comprising DNA hybridizing to thecomplement of the nucleic acid between about residues 63 or 117 andabout 867, inclusive, of FIG. 150 (SEQ ID NO:222). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203025(DNA57836-1338), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203025 (DNA57836-1338).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 1 or 19 to about 265, inclusive of FIG. 151(SEQ ID NO:223), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule produced by hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO809 polypeptide havingthe sequence of amino acid residues from about 1 or 19 to about 265,inclusive of FIG. 151 (SEQ ID NO:223), or (b) the complement of the DNAmolecule of (a), and, if the DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), isolating the testDNA molecule.

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 19 to about 265, inclusive of FIG. 151 (SEQ ID NO:223), or (b) thecomplement of the DNA of (a).

In another embodiment, the invention provides isolated PRO809polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO809 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 or 19 through 265 of FIG. 151 (SEQ IDNO:223).

In another aspect, the invention concerns an isolated PRO809polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 19 to about 265, inclusive of FIG. 151 (SEQ ID NO:223).

In a further aspect, the invention concerns an isolated PRO809polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 19through 265 of FIG. 151 (SEQ ID NO:223).

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO809 polypeptide having the sequence ofamino acid residues from about 1 or 19 to about 265, inclusive of FIG.151 (SEQ ID NO:223), or (b) the complement of the DNA molecule of (a),and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO809 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO809 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO809 polypeptide, by contactingthe native PRO809 polypeptide with a candidate molecule and monitoring abiological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO809 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

62. PRO791

A cDNA clone (DNA57838-1337) has been identified, having sequenceidentity with MHC class I antigens that encodes a novel polypeptide,designated in the present application as “PRO791.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO791 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO791 polypeptide having the sequence of amino acid residuesfrom about 1 or 26 to about 246, inclusive of FIG. 153 (SEQ ID NO:225),or (b) the complement of the DNA molecule of (a). The term “or” as usedherein to refer to amino or nucleic acids is meant to refer to twoalternative embodiments provided herein, i.e., 1–246, or in anotherembodiment, 26–246.

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO791 polypeptide comprising DNA hybridizing to thecomplement of the nucleic acid between about residues 9 or 84 and about746, inclusive, of FIG. 152 (SEQ ID NO:224). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203014(DNA57838-1337), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203014 (DNA57838-1337).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 1 or 26 to about 246, inclusive of FIG. 153(SEQ ID NO:225), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule produced by hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO791 polypeptide havingthe sequence of amino acid residues from about 1 or 26 to about 246,inclusive of FIG. 153 (SEQ ID NO:225), or (b) the complement of the DNAmolecule of (a), and, if the DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), isolating the testDNA molecule.

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 26 to about 246, inclusive of FIG. 153 (SEQ ID NO:225), or (b) thecomplement of the DNA of (a).

In another embodiment, the invention provides isolated PRO791polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO791 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 or 26 through 246 of FIG. 153 (SEQ IDNO:225).

In another aspect, the invention concerns an isolated PRO791polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 26 to about 246, inclusive of FIG. 153 (SEQ ID NO:225).

In a further aspect, the invention concerns an isolated PRO791polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 26through 246 of FIG. 153 (SEQ ID NO:225).

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO791 polypeptide having the sequence ofamino acid residues from about 1 or 26 to about 246, inclusive of FIG.153 (SEQ ID NO:225), or (b) the complement of the DNA molecule of (a),and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO791 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO791 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO791 polypeptide, by contactingthe native PRO791 polypeptide with a candidate molecule and monitoring abiological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO791 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

63. PRO1004

A cDNA clone (DNA57844-1410) has been identified that encodes a novelpolypeptide, designated in the present application as “PRO1004.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1004 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1004 polypeptide having the sequence of amino acidresidues from about 25 to about 115, inclusive of FIG. 155 (SEQ IDNO:227), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1004 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 191 and about463, inclusive, of FIG. 154 (SEQ ID NO:226). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203010(DNA57844-1410), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203010 (DNA57844-1410).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 25 to about 115, inclusive of FIG. 155 (SEQ IDNO:227), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least 50 nucleotides, and preferably at least 100nucleotides, and produced by hybridizing a test DNA molecule understringent conditions with (a) a DNA molecule encoding a PRO1004polypeptide having the sequence of amino acid residues from about 25 toabout 115, inclusive of FIG. 155 (SEQ ID NO:227), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least aboutan 80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1004 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, or iscomplementary to such encoding nucleic acid molecule. The signal peptidehas been tentatively identified as extending from about amino acidposition 1 through about amino acid position 24 in the sequence of FIG.155 (SEQ ID NO:227).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 25to about 115, inclusive of FIG. 155 (SEQ ID NO:227), or (b) thecomplement of the DNA of (a).

Another embodiment of the invention is directed to fragments of aPRO1004 polypeptide coding sequence that may find use as hybridizationprobes. Such nucleic acid fragments are from about 20 to about 80nucleotides in length, preferably from about 20 to about 60 nucleotidesin length, more preferably from about 20 to about 50 nucleotides inlength, and most preferably from about 20 to about 40 nucleotides inlength.

In another embodiment, the invention provides isolated PRO1004polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1004 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 25 to 115 of FIG. 155 (SEQ ID NO:227).

In another aspect, the invention concerns an isolated PRO1004polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues25 to about 115, inclusive of FIG. 155 (SEQ ID NO:227).

In a further aspect, the invention concerns an isolated PRO1004polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 25 to115 of FIG. 155 (SEQ ID NO:227).

In yet another aspect, the invention concerns an isolated PRO1004polypeptide, comprising the sequence of amino acid residues 25 to about115, inclusive of FIG. 155 (SEQ ID NO:227), or a fragment thereofsufficient to provide a binding site for an anti-PRO1004 antibody.Preferably, the PRO1004 fragment retains a qualitative biologicalactivity of a native PRO1004 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1004 polypeptide having the sequence ofamino acid residues from about 25 to about 115, inclusive of FIG. 155(SEQ ID NO:227), or (b) the complement of the DNA molecule of (a), andif the test DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

64. PRO1111

A cDNA clone (DNA58721-1475) has been identified that encodes a novelpolypeptide having sequence identity with LIG and designated in thepresent application as “PRO1111.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1111 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1111 polypeptide having the sequence of amino acidresidues from about 1 to about 653, inclusive of FIG. 157 (SEQ IDNO:229), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1111 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 57 and about2015, inclusive, of FIG. 156 (SEQ ID NO:228). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203110(DNA58721-1475), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203110 (DNA58721-1475).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 1 to about 653, inclusive of FIG. 157 (SEQ IDNO:229), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least about 50 nucleotides, and preferably at leastabout 100 nucleotides and produced by hybridizing a test DNA moleculeunder stringent conditions with (a) a DNA molecule encoding a PRO1111polypeptide having the sequence of amino acid residues from about 1 toabout 653, inclusive of FIG. 157 (SEQ ID NO:229), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least aboutan 80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1111 polypeptide in its solubleform, i.e. transmembrane domain deleted or inactivated variants, or iscomplementary to such encoding nucleic acid molecule. The transmembranedomains has been tentatively identified as extending from about aminoacid positions 21–40 (type II) and 528–548 in the PRO1111 amino acidsequence (FIG. 157, SEQ ID NO:229).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1to about 653, inclusive of FIG. 157 (SEQ ID NO:229), or (b) thecomplement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1111 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1111polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1111 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 through 653 of FIG. 157 (SEQ ID NO:229).

In another aspect, the invention concerns an isolated PRO1111polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 to about 653, inclusive of FIG. 157 (SEQ ID NO:229).

In a further aspect, the invention concerns an isolated PRO1111polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1through 653 of FIG. 157 (SEQ ID NO:229).

In yet another aspect, the invention concerns an isolated PRO1111polypeptide, comprising the sequence of amino acid residues 1 to about653, inclusive of FIG. 157 (SEQ ID NO:229), or a fragment thereofsufficient to provide a binding site for an anti-PRO1111 antibody.Preferably, the PRO1111 fragment retains a qualitative biologicalactivity of a native PRO1111 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1111 polypeptide having the sequence ofamino acid residues from about 1 to about 653, inclusive of FIG. 157(SEQ ID NO:229), or (b) the complement of the DNA molecule of (a), andif the test DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1111 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1111 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1111 polypeptide, by contactingthe native PRO1111 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1111 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

65. PRO1344

A cDNA clone (DNA58723-1588) has been identified, having homology tonucleic acid encoding factor C that encodes a novel polypeptide,designated in the present application as “PRO1344”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1344 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1344 polypeptide having the sequence of amino acidresidues from about 1 or about 24 to about 720, inclusive of FIG. 159(SEQ ID NO:231), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1344 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about nucleotides 26 or about95 and about 2185, inclusive, of FIG. 158 (SEQ ID NO:230). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203133(DNA58723-1588) or (b) the complement of the nucleic acid molecule of(a). In a preferred embodiment, the nucleic acid comprises a DNAencoding the same mature polypeptide encoded by the human protein cDNAin ATCC Deposit No. 203133 (DNA58723-1588).

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 24 to about 720, inclusive of FIG. 159 (SEQ IDNO:231), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least 10 nucleotides and produced by hybridizing atest DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1344 polypeptide having the sequence of amino acidresidues from 1 or about 24 to about 720, inclusive of FIG. 159 (SEQ IDNO:231), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, preferably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1344 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, or iscomplementary to such encoding nucleic acid molecule. The signal peptidehas been tentatively identified as extending from about amino acidposition 1 to about amino acid position 23 in the sequence of FIG. 159(SEQ ID NO:231).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 24 to about 720, inclusive of FIG. 159 (SEQ ID NO:231), or (b)the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1344 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 158 (SEQ ID NO:230).

In another embodiment, the invention provides isolated PRO1344polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO1344 polypeptide, which in certain embodiments, includes an aminoacid sequence comprising residues 1 or about 24 to about 720 of FIG. 159(SEQ ID NO:231).

In another aspect, the invention concerns an isolated PRO1344polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 24 to about 720, inclusive of FIG. 159 (SEQ ID NO:231).

In a further aspect, the invention concerns an isolated PRO1344polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 24 to about 720, inclusive of FIG. 159 (SEQ ID NO:231).

In yet another aspect, the invention concerns an isolated PRO1344polypeptide, comprising the sequence of amino acid residues 1 or about24 to about 720, inclusive of FIG. 159 (SEQ ID NO:231), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1344antibody. Preferably, the PRO1344 fragment retains a qualitativebiological activity of a native PRO1344 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1344 polypeptide having the sequence ofamino acid residues from about 1 or about 24 to about 720, inclusive ofFIG. 159 (SEQ ID NO:231), or (b) the complement of the DNA molecule of(a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1344 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1344 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1344 polypeptide by contactingthe native PRO1344 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1344 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

66. PRO1109

A cDNA clone (DNA58737-1473) has been identified, having homology tonucleic acid encoding β-1,4-galactosyltransferase, that encodes a novelpolypeptide, designated in the present application as “PRO1109”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1109 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1109 polypeptide having the sequence of amino acidresidues from about 1 or about 28 to about 344, inclusive of FIG. 161(SEQ ID NO:236), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1109 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about nucleotides 119 orabout 200 and about 1150, inclusive, of FIG. 160 (SEQ ID NO:235).Preferably, hybridization occurs under stringent hybridization and washconditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203136(DNA58737-1473) or (b) the complement of the nucleic acid molecule of(a). In a preferred embodiment, the nucleic acid comprises a DNAencoding the same mature polypeptide encoded by the human protein cDNAin ATCC Deposit No. 203136 (DNA58737-1473).

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 28 to about 344, inclusive of FIG. 161 (SEQ IDNO:236), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least 10 nucleotides and produced by hybridizing atest DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1109 polypeptide having the sequence of amino acidresidues from 1 or about 28 to about 344, inclusive of FIG. 161 (SEQ IDNO:236), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, preferably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1109 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, or iscomplementary to such encoding nucleic acid molecule. The signal peptidehas been tentatively identified as extending from about amino acidposition 1 to about amino acid position 27 in the sequence of FIG. 161(SEQ ID NO:236).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 28 to about 344, inclusive of FIG. 161 (SEQ ID NO:236), or (b)the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1109 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 160 (SEQ ID NO:235).

In another embodiment, the invention provides isolated PRO1109polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO1109 polypeptide, which in certain embodiments, includes an aminoacid sequence comprising residues 1 or about 28 to about 344 of FIG. 161(SEQ ID NO:236).

In another aspect, the invention concerns an isolated PRO1109polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 28 to about 344, inclusive of FIG. 161 (SEQ ID NO:236).

In a further aspect, the invention concerns an isolated PRO1109polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 28 to about 344, inclusive of FIG. 161 (SEQ ID NO:236).

In yet another aspect, the invention concerns an isolated PRO1109polypeptide, comprising the sequence of amino acid residues 1 or about28 to about 344, inclusive of FIG. 161 (SEQ ID NO:236), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1109antibody. Preferably, the PRO1109 fragment retains a qualitativebiological activity of a native PRO1109 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1109 polypeptide having the sequence ofamino acid residues from about 1 or about 28 to about 344, inclusive ofFIG. 161 (SEQ ID NO:236), or (b) the complement of the DNA molecule of(a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (ii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1109 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1109 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1109 polypeptide by contactingthe native PRO1109 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1109 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

67. PRO1383

A cDNA clone (DNA58743-1609) has been identified, having homology tonucleic acid encoding the human melanoma cell-expressed protein nmb,that encodes a novel polypeptide, designated in the present applicationas “PRO1383”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1383 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1383 polypeptide having the sequence of amino acidresidues from about 1 or about 25 to about 423, inclusive of FIG. 163(SEQ ID NO:241), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1383 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about nucleotides 122 orabout 194 and about 1390, inclusive, of FIG. 162 (SEQ ID NO:240).Preferably, hybridization occurs under stringent hybridization and washconditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203154(DNA58743-1609) or (b) the complement of the nucleic acid molecule of(a). In a preferred embodiment, the nucleic acid comprises a DNAencoding the same mature polypeptide encoded by the human protein cDNAin ATCC Deposit No. 203154 (DNA58743-1609).

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 25 to about 423, inclusive of FIG. 163 (SEQ IDNO:241), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least 10 nucleotides and produced by hybridizing atest DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1383 polypeptide having the sequence of amino acidresidues from 1 or about 25 to about 423, inclusive of FIG. 163 (SEQ IDNO:241), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, preferably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1383 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, and itssoluble, i.e., transmembrane domain deleted or inactivated variants, oris complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from about aminoacid position 1 to about amino acid position 24 in the sequence of FIG.163 (SEQ ID NO:241). The transmembrane domain has been tentativelyidentified as extending from about amino acid position 339 to aboutamino acid position 362 in the PRO1383 amino acid sequence (FIG. 163,SEQ ID NO:241).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 25 to about 423, inclusive of FIG. 163 (SEQ ID NO:241), or (b)the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1383 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 162 (SEQ ID NO:240).

In another embodiment, the invention provides isolated PRO1383polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO1383 polypeptide, which in certain embodiments, includes an aminoacid sequence comprising residues 1 or about 25 to about 423 of FIG. 163(SEQ ID NO:241).

In another aspect, the invention concerns an isolated PRO1383polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 25 to about 423, inclusive of FIG. 163 (SEQ ID NO:241).

In a further aspect, the invention concerns an isolated PRO1383polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 25 to about 423, inclusive of FIG. 163 (SEQ ID NO:241).

In yet another aspect, the invention concerns an isolated PRO1383polypeptide, comprising the sequence of amino acid residues 1 or about25 to about 423, inclusive of FIG. 163 (SEQ ID NO:241), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1383antibody. Preferably, the PRO1383 fragment retains a qualitativebiological activity of a native PRO1383 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1383 polypeptide having the sequence ofamino acid residues from about 1 or about 25 to about 423, inclusive ofFIG. 163 (SEQ ID NO:241), or (b) the complement of the DNA molecule of(a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1383 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1383 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1383 polypeptide by contactingthe native PRO1383 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1383 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

68. PRO1003

Applicants have identified a cDNA clone, DNA58846-1409, that encodes anovel secreted polypeptide wherein the polypeptide is designated in thepresent application as “PRO1003”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1003 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1003 polypeptide having the sequence of amino acidresidues from 1 or about 25 to about 84, inclusive of FIG. 165 (SEQ IDNO:246), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1003 polypeptide comprising DNA that hybridizesto the complement of the nucleic acid between about residues 41 or about113 and about 292 inclusive of FIG. 164 (SEQ ID NO:245). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 209957(DNA58846-1409), which was deposited on Jun. 9, 1998. In a preferredembodiment, the nucleic acid comprises a DNA molecule encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.209957 (DNA58846-1409).

In an additional aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA encoding a polypeptide having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 25 to about 84, inclusive of FIG. 165 (SEQ ID NO:246).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA encoding a polypeptide scoring at least about80% positives, preferably at least about 90% positives, most preferablyat least about 95% positives when compared with the amino acid sequenceof residues 1 or about 25 to about 84, inclusive of FIG. 165 (SEQ IDNO:246).

Another embodiment is directed to fragments of a PRO1003 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1003polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO1003 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 or about 25 to 84 of FIG. 165 (SEQ IDNO:246).

In another aspect, the invention concerns an isolated PRO1003polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 25 to 84, inclusive of FIG. 165 (SEQ ID NO:246).

In a further aspect, the invention concerns an isolated PRO1003polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 25 to about 84 of FIG. 165 (SEQ ID NO:246).

In yet another aspect, the invention concerns an isolated PRO1003polypeptide, comprising the sequence of amino acid residues 1 or about25 to about 84, inclusive of FIG. 165 (SEQ ID NO:246), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1003antibody. Preferably, the PRO1003 fragment retains a qualitativebiological activity of a native PRO1003 polypeptide.

In another aspect, the present invention is directed to fragments of aPRO1003 polypeptide which are sufficiently long to provide an epitopeagainst which an antibody may be generated.

69. PRO1108

Applicants have identified a cDNA clone (DNA58848-1472) having homologyto nucleic acid encoding the LPAAT protein that encodes a novelpolypeptide, designated in the present application as “PRO1108”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1108 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1108 polypeptide having the sequence of amino acidresidues from about 1 to about 456, inclusive of FIG. 167 (SEQ IDNO:248), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1108 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about nucleotides 77 andabout 1444, inclusive, of FIG. 166 (SEQ ID NO:247). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 209955(DNA58848-1472). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 209955 (DNA58848-1472).

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 to about 456, inclusive of FIG. 167 (SEQ ID NO:248).

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1108 polypeptide, with or withoutthe initiating methionine, and its soluble, i.e., transmembrane domaindeleted or inactivated variants, or is complementary to such encodingnucleic acid molecule. The transmembrane domains have been tentativelyidentified as being type II domains extending from about amino acidposition 22 to about amino acid position 42, from about amino acidposition 156 to about amino acid position 176, from about amino acidposition 180 to about amino acid position 199 and from about amino acidposition 369 to about amino acid position 388 in the PRO1108 amino acidsequence (FIG. 167, SEQ ID NO:248).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA encoding a polypeptide scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 toabout 456, inclusive of FIG. 167 (SEQ ID NO:248).

Another embodiment is directed to fragments of a PRO1108 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1108polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO1108 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 to about 456 of FIG. 167 (SEQ ID NO:248).

In another aspect, the invention concerns an isolated PRO1108polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 to about 456, inclusive of FIG. 167 (SEQ ID NO:248).

In a further aspect, the invention concerns an isolated PRO1108polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 toabout 456, inclusive of FIG. 167 (SEQ ID NO:248).

In yet another aspect, the invention concerns an isolated PRO1108polypeptide, comprising the sequence of amino acid residues 1 to about456, inclusive of FIG. 167 (SEQ ID NO:248), or a fragment thereofsufficient to provide a binding site for an anti-PRO1108 antibody.Preferably, the PRO1108 fragment retains a qualitative biologicalactivity of a native PRO1108 polypeptide.

In another aspect, the present invention is directed to fragments of aPRO1108 polypeptide which are sufficiently long to provide an epitopeagainst which an antibody may be generated.

In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1108 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1108 antibody.

In a further embodiment, the invention concerns screening assays toidentify agonists or antagonists of a native PRO1108 polypeptide.

In still a further embodiment, the invention concerns a compositioncomprising a PRO1108 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

70. PRO1137

Applicants have identified a cDNA clone, DNA58849-1494, that encodes anovel polypeptide having homology to ribosyltransferase wherein thepolypeptide is designated in the present application as “PRO1137”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1137 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, and mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1137 polypeptide having the sequence of amino acidresidues from 1 or about 15 to about 240, inclusive of FIG. 169 (SEQ IDNO:250), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1137 polypeptide comprising DNA that hybridizesto the complement of the nucleic acid sequence having about residues 77or about 119 to about 796, inclusive of FIG. 168 (SEQ ID NO:249).Preferably, hybridization occurs under stringent hybridization and washconditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, and most preferably at least about95% sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 209958(DNA58849-1494), which was deposited on Jun. 9, 1998, or (b) thecomplement of the DNA molecule of (a).

In a preferred embodiment, the nucleic acid comprises a DNA moleculeencoding the same mature polypeptide encoded by the human protein cDNAin ATCC Deposit No. 209958 (DNA58849-1494).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, and mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 15 to about 240, inclusive of FIG. 169 (SEQ IDNO:250).

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1137 polypeptide with or withoutthe N-terminal signal sequence and/or the initiating methionine, or thecomplement of such encoding DNA molecule. The signal peptide has beententatively identified as extending from about amino acid position 1 toabout amino acid position 14 in the sequence of FIG. 169 (SEQ IDNO:250).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA encoding a polypeptide scoring at least about80% positives, preferably at least about 90% positives, and mostpreferably at least about 95% positives when compared with the aminoacid sequence of residues 1 or about 15 to about 240, inclusive of FIG.169 (SEQ ID NO:250).

Another embodiment is directed to fragments of a PRO1137 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1137polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO1137 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 or about 15 to 240 of FIG. 169 (SEQ IDNO:250).

In another aspect, the invention concerns an isolated PRO1137polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, and most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 15 to 240, inclusive of FIG. 169 (SEQ ID NO:250).

In a further aspect, the invention concerns an isolated PRO1137polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, and most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 15 to about 240 of FIG. 169 (SEQ ID NO:250).

In yet another aspect, the invention concerns an isolated PRO1137polypeptide, comprising the sequence of amino acid residues 1 or about15 to about 240, inclusive of FIG. 169 (SEQ ID NO:250), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1137antibody. Preferably, the PRO1137 fragment retains a qualitativebiological activity of a native PRO1137 polypeptide.

In another aspect, the present invention is directed to fragments of aPRO1137 polypeptide which are sufficiently long to provide an epitopeagainst which an antibody may be generated.

In yet another embodiment, the invention concerns agonist andantagonists of the PRO1137 polypeptide. In a particular embodiment, theagonist or antagonist is an anti-PRO1137 antibody.

In a further embodiment, the invention concerns screening assays toidentify agonists or antagonists of a native PRO1137 polypeptide.

In still a further embodiment, the invention concerns a compositioncomprising a PRO1137 polypeptide as hereinabove defined, in combinationwith a pharmaceutically acceptable carrier.

71. PRO1138

Applicants have identified a cDNA clone, DNA58850-1495, that encodes anovel polypeptide having homology to CD84 leukocyte antigen wherein thepolypeptide is designated in the present application as “PRO1138”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1138 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, and mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1138 polypeptide having the sequence of amino acidresidues from 1 or about 23 to about 335, inclusive of FIG. 171 (SEQ IDNO:253), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1138 polypeptide comprising DNA that hybridizesto the complement of the nucleic acid sequence having about residues 38or about 104 to about 1042, inclusive of FIG. 170 (SEQ ID NO:252).Preferably, hybridization occurs under stringent hybridization and washconditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, and most preferably at least about95% sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 209956(DNA58850-1495), which was deposited on Jun. 9, 1998, or (b) thecomplement of the DNA molecule of (a). In a preferred embodiment, thenucleic acid comprises a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 209956(DNA58850-1495).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, and mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 23 to about 335, inclusive of FIG. 171 (SEQ IDNO:253).

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1138 extracellular domain (ECD),with or without the N-terminal signal sequence and/or the initiatingmethionine, and its soluble variants (i.e. transmembrane domain(s)deleted or inactivated) or is complementary to such encoding nucleicacid molecule. The signal peptide has been tentatively identified asextending from amino acid position 1 to about amino acid position 22 inthe sequence of FIG. 171 (SEQ ID NO:253). A transmembrane domain regionhas been tentatively identified as extending from about amino acidposition 224 to about amino acid position 250 in the PRO1138 amino acidsequence (FIG. 171, SEQ ID NO:253).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA encoding a polypeptide scoring at least about80% positives, preferably at least about 90% positives, and mostpreferably at least about 95% positives when compared with the aminoacid sequence of residues 1 or about 23 to about 335, inclusive of FIG.171 (SEQ ID NO:253).

Another embodiment is directed to fragments of a PRO1138 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1138polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO1138 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 or about 23 to 335 of FIG. 171 (SEQ IDNO:253).

In another aspect, the invention concerns an isolated PRO1138polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, and most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 23 to 335, inclusive of FIG. 171 (SEQ ID NO:253).

In a further aspect, the invention concerns an isolated PRO1138polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, and most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 23 to about 335 of FIG. 171 (SEQ ID NO:253).

In another aspect, the invention concerns a PRO1138 extracellular domaincomprising an amino acid sequence having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, and most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 23 to X of FIG. 171 (SEQ ID NO:253), wherein X is any one ofamino acid residues 219 to 228 of FIG. 171 (SEQ ID NO:253).

In yet another aspect, the invention concerns an isolated PRO1138polypeptide, comprising the sequence of amino acid residues 1 or about23 to about 335, inclusive of FIG. 171 (SEQ ID NO:253), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1138antibody. Preferably, the PRO1138 fragment retains a qualitativebiological activity of a native PRO1138 polypeptide.

In another aspect, the present invention is directed to fragments of aPRO1138 polypeptide which are sufficiently long to provide an epitopeagainst which an antibody may be generated.

In yet another embodiment, the invention concerns agonist andantagonists of the PRO1138 polypeptide. In a particular embodiment, theagonist or antagonist is an anti-PRO1138 antibody.

In a further embodiment, the invention concerns screening assays toidentify agonists or antagonists of a native PRO1138 polypeptide.

In still a further embodiment, the invention concerns a compositioncomprising a PRO1138 polypeptide as hereinabove defined, in combinationwith a pharmaceutically acceptable carrier.

In another embodiment, the invention provides a nucleotide sequencedesignated herein as DNA49140 comprising the nucleotide sequence of FIG.172 (SEQ ID NO:254).

72. PRO1054

A cDNA clone (DNA58853-1423) has been identified, having homology tonucleic acid encoding major urinary proteins (MUPs) that encodes a novelpolypeptide, designated in the present application as “PRO1054”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1054 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1054 polypeptide having the sequence of amino acidresidues from about 1 or about 19 to about 180, inclusive of FIG. 174(SEQ ID NO:256), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1054 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about nucleotides 46 or about100 and about 585, inclusive, of FIG. 173 (SEQ ID NO:255). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203016(DNA58853-1423) or (b) the complement of the nucleic acid molecule of(a). In a preferred embodiment, the nucleic acid comprises a DNAencoding the same mature polypeptide encoded by the human protein cDNAin ATCC Deposit No. 203016 (DNA58853-1423).

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 19 to about 180, inclusive of FIG. 174 (SEQ IDNO:256), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least 10 nucleotides and produced by hybridizing atest DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1054 polypeptide having the sequence of amino acidresidues from 1 or about 19 to about 180, inclusive of FIG. 174 (SEQ IDNO:256), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, preferably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1054 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, or iscomplementary to such encoding nucleic acid molecule. The signal peptidehas been tentatively identified as extending from about amino acidposition 1 to about amino acid position 18 in the sequence of FIG. 174(SEQ ID NO:256).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 19 to about 180, inclusive of FIG. 174 (SEQ ID NO:256), or (b)the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1054 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 173 (SEQ ID NO:255).

In another embodiment, the invention provides isolated PRO1054polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO1054 polypeptide, which in certain embodiments, includes an aminoacid sequence comprising residues 1 or about 19 to about 180 of FIG. 174(SEQ ID NO:256).

In another aspect, the invention concerns an isolated PRO1054polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 19 to about 180, inclusive of FIG. 174 (SEQ ID NO:256).

In a further aspect, the invention concerns an isolated PRO1054polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 19 to about 180, inclusive of FIG. 174 (SEQ ID NO:256).

In yet another aspect, the invention concerns an isolated PRO1054polypeptide, comprising the sequence of amino acid residues 1 or about19 to about 180, inclusive of FIG. 174 (SEQ ID NO:256), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1054antibody. Preferably, the PRO1054 fragment retains a qualitativebiological activity of a native PRO1054 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1054 polypeptide having the sequence ofamino acid residues from about 1 or about 19 to about 180, inclusive ofFIG. 174 (SEQ ID NO:256), or (b) the complement of the DNA molecule of(a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1054 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1054 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1054 polypeptide by contactingthe native PRO1054 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1054 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

73. PRO994

A cDNA clone (DNA58855-1422) has been identified, having homology tonucleic acid encoding the tumor-associated antigen L6 that encodes anovel polypeptide, designated in the present application as “PRO994”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO994 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO994 polypeptide having the sequence of amino acid residuesfrom about 1 to about 229, inclusive of FIG. 176 (SEQ ID NO:258), or (b)the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO994 polypeptide comprising DNA hybridizing to thecomplement of the nucleic acid between about nucleotides 31 and about717, inclusive, of FIG. 175 (SEQ ID NO:257). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203018(DNA58855-1422) or (b) the complement of the nucleic acid molecule of(a). In a preferred embodiment, the nucleic acid comprises a DNAencoding the same mature polypeptide encoded by the human protein cDNAin ATCC Deposit No. 203018 (DNA58855-1422).

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 to about 229, inclusive of FIG. 176 (SEQ ID NO:258), or(b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least 10 nucleotides and produced by hybridizing atest DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO994 polypeptide having the sequence of amino acid residuesfrom 1 to about 229, inclusive of FIG. 176 (SEQ ID NO:258), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO994 polypeptide, with or withoutthe initiating methionine, and its soluble, i.e., transmembrane domaindeleted or inactivated variants, or is complementary to such encodingnucleic acid molecule. The multiple transmembrane domains have beententatively identified as extending from about amino acid position 10 toabout amino acid position 31, from about amino acid position 50 to aboutamino acid position 72, from about amino acid position 87 to about aminoacid position 110 and from about amino acid position 191 to about aminoacid position 213 in the PRO994 amino acid sequence (FIG. 176, SEQ IDNO:258).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1to about 229, inclusive of FIG. 176 (SEQ ID NO:258), or (b) thecomplement of the DNA of (a).

Another embodiment is directed to fragments of a PRO994 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 175 (SEQ ID NO:257).

In another embodiment, the invention provides isolated PRO994polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO994 polypeptide, which in certain embodiments, includes an amino acidsequence comprising residues 1 to about 229 of FIG. 176 (SEQ ID NO:258).

In another aspect, the invention concerns an isolated PRO994polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 to about 229, inclusive of FIG. 176 (SEQ ID NO:258).

In a further aspect, the invention concerns an isolated PRO994polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 toabout 229, inclusive of FIG. 176 (SEQ ID NO:258).

In yet another aspect, the invention concerns an isolated PRO994polypeptide, comprising the sequence of amino acid residues 1 to about229, inclusive of FIG. 176 (SEQ ID NO:258), or a fragment thereofsufficient to provide a binding site for an anti-PRO994 antibody.Preferably, the PRO994 fragment retains a qualitative biologicalactivity of a native PRO994 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO994 polypeptide having the sequence ofamino acid residues from about 1 to about 229, inclusive of FIG. 176(SEQ ID NO:258), or (b) the complement of the DNA molecule of (a), andif the test DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of a native PRO994 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO994 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO994 polypeptide by contacting thenative PRO994 polypeptide with a candidate molecule and monitoring abiological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO994 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

74. PRO812

A cDNA clone (DNA59205-1421) has been identified, having homology tonucleic acid encoding prostatic steroid-binding protein cl that encodesa novel polypeptide, designated in the present application as “PRO812”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO812 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO812 polypeptide having the sequence of amino acid residuesfrom about 1 or about 16 to about 83, inclusive of FIG. 178 (SEQ IDNO:260), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO812 polypeptide comprising DNA hybridizing to thecomplement of the nucleic acid between about nucleotides 55 or about 100and about 303, inclusive, of FIG. 177 (SEQ ID NO:259). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203009(DNA59205-1421) or (b) the complement of the nucleic acid molecule of(a). In a preferred embodiment, the nucleic acid comprises a DNAencoding the same mature polypeptide encoded by the human protein cDNAin ATCC Deposit No. 203009 (DNA59205-1421).

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 16 to about 83, inclusive of FIG. 178 (SEQ IDNO:260), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least 100 nucleotides and produced by hybridizing atest DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO812 polypeptide having the sequence of amino acid residuesfrom 1 or about 16 to about 83, inclusive of FIG. 178 (SEQ ID NO:260),or (b) the complement of the DNA molecule of (a), and, if the DNAmolecule has at least about an 80% sequence identity, preferably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO812 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, or iscomplementary to such encoding nucleic acid molecule. The signal peptidehas been tentatively identified as extending from about amino acidposition 1 to about amino acid position 15 in the sequence of FIG. 178(SEQ ID NO:260).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 16 to about 83, inclusive of FIG. 178 (SEQ ID NO:260), or (b)the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO812 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 177 (SEQ ID NO:259).

In another embodiment, the invention provides isolated PRO812polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO812 polypeptide, which in certain embodiments, includes an amino acidsequence comprising residues 1 or about 16 to about 83 of FIG. 178 (SEQID NO:260).

In another aspect, the invention concerns an isolated PRO812polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 16 to about 83, inclusive of FIG. 178 (SEQ ID NO:260).

In a further aspect, the invention concerns an isolated PRO812polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 16 to about 83, inclusive of FIG. 178 (SEQ ID NO:260).

In yet another aspect, the invention concerns an isolated PRO812polypeptide, comprising the sequence of amino acid residues 1 or about16 to about 83, inclusive of FIG. 178 (SEQ ID NO:260), or a fragmentthereof sufficient to provide a binding site for an anti-PRO812antibody. Preferably, the PRO812 fragment retains a qualitativebiological activity of a native PRO812 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO812 polypeptide having the sequence ofamino acid residues from about 1 or about 16 to about 83, inclusive ofFIG. 178 (SEQ ID NO:260), or (b) the complement of the DNA molecule of(a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of a native PRO812 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO812 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO812 polypeptide by contacting thenative PRO812 polypeptide with a candidate molecule and monitoring abiological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO812 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

75. PRO1069

Applicants have identified a cDNA clone, DNA59211-1450, that encodes anovel polypeptide having homology to CHIF wherein the polypeptide isdesignated in the present application as “PRO1069”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1069 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1069 polypeptide having the sequence of amino acidresidues from 1 or about 17 to about 89, inclusive of FIG. 180 (SEQ IDNO:262), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1069 polypeptide comprising DNA that hybridizesto the complement of the nucleic acid sequence having about residues 197or about 245 to about 463, inclusive of FIG. 179 (SEQ ID NO:261).Preferably, hybridization occurs under stringent hybridization and washconditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 209960(DNA59211-1450), which was deposited on Jun. 9, 1998. In a preferredembodiment, the nucleic acid comprises a DNA molecule encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.209960 (DNA59211-1450).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 17 to about 89, inclusive of FIG. 180 (SEQ IDNO:262).

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1069 extracellular domain (ECD),with or without the N-terminal signal sequence and/or the initiatingmethionine, and its soluble variants (i.e. transmembrane domain(s)deleted or inactivated) or is complementary to such encoding nucleicacid molecule. The signal peptide has been tentatively identified asextending from amino acid position 1 to about amino acid position 16 inthe sequence of FIG. 180 (SEQ ID NO:262). A transmembrane domain regionhas been tentatively identified as extending from about amino acidposition 36 to about amino acid position 59 in the PRO1069 amino acidsequence (FIG. 180, SEQ ID NO:262).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA encoding a polypeptide scoring at least about80% positives, preferably at least about 90% positives, most preferablyat least about 95% positives when compared with the amino acid sequenceof residues 1 or about 17 to about 89, inclusive of FIG. 180 (SEQ IDNO:262).

Another embodiment is directed to fragments of a PRO1069 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1069polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO1069 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 or about 17 to 89 of FIG. 180 (SEQ IDNO:262).

In another aspect, the invention concerns an isolatedPRO1069polypeptide, comprising an amino acid sequence having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 17 to 89, inclusive of FIG. 180 (SEQ IDNO:262).

In a further aspect, the invention concerns an isolated PRO1069polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 17 to about 89 of FIG. 180 (SEQ ID NO:262).

In another aspect, the invention concerns a PRO1069 extracellular domaincomprising an amino acid sequence having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 17 to X of FIG. 180 (SEQ ID NO:262), wherein X is any one ofamino acid residues 32 to 41 of FIG. 180 (SEQ ID NO:262).

In yet another aspect, the invention concerns an isolated PRO1069polypeptide, comprising the sequence of amino acid residues 1 or about17 to about 89, inclusive of FIG. 180 (SEQ ID NO:262), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1069antibody. Preferably, the PRO1069 fragment retains a qualitativebiological activity of a native PRO1069 polypeptide.

In another aspect, the present invention is directed to fragments of aPRO1069 polypeptide which are sufficiently long to provide an epitopeagainst which an antibody may be generated.

In yet another embodiment, the invention concerns agonist andantagonists of the PRO1069 polypeptide. In a particular embodiment, theagonist or antagonist is an anti-PRO1069 antibody.

In a further embodiment, the invention concerns screening assays toidentify agonists or antagonists of a native PRO1069 polypeptide.

In still a further embodiment, the invention concerns a compositioncomprising a PRO1069 polypeptide as hereinabove defined, in combinationwith a pharmaceutically acceptable carrier.

76. PRO1129

Applicants have identified a cDNA clone (DNA59213-1487) having homologyto nucleic acid encoding cytochrome P-450 family members that encodes anovel polypeptide, designated in the present application as “PRO1129”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1129 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1129 polypeptide having the sequence of amino acidresidues from about 1 to about 524, inclusive of FIG. 182 (SEQ IDNO:264), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1129 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about nucleotides 42 andabout 1613, inclusive, of FIG. 181 (SEQ ID NO:263). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 209959(DNA59213-1487). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 209959 (DNA59213-1487).

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 to about 524, inclusive of FIG. 182 (SEQ ID NO:264).

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1129 polypeptide, with or withoutthe initiating methionine, and its soluble, i.e., transmembrane domaindeleted or inactivated variants, or is complementary to such encodingnucleic acid molecule. The type II transmembrane domains have beententatively identified as extending from about amino acid position 13 toabout amino acid position 32 and from about amino acid position 77 toabout amino acid position 102 in the PRO1129 amino acid sequence (FIG.182, SEQ ID NO:264).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA encoding a polypeptide scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 toabout 524, inclusive of FIG. 182 (SEQ ID NO:264).

Another embodiment is directed to fragments of a PRO1129 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1129polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO1129 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 to about 524 of FIG. 182 (SEQ ID NO:264).

In another aspect, the invention concerns an isolated PRO1129polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 to about 524, inclusive of FIG. 182 (SEQ ID NO:264).

In a further aspect, the invention concerns an isolated PRO1129polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 toabout 524, inclusive of FIG. 182 (SEQ ID NO:264).

In yet another aspect, the invention concerns an isolated PRO1129polypeptide, comprising the sequence of amino acid residues 1 to about524, inclusive of FIG. 182 (SEQ ID NO:264), or a fragment thereofsufficient to provide a binding site for an anti-PRO1129 antibody.Preferably, the PRO1129 fragment retains a qualitative biologicalactivity of a native PRO1129 polypeptide.

In another aspect, the present invention is directed to fragments of aPRO1129 polypeptide which are sufficiently long to provide an epitopeagainst which an antibody may be generated.

In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1129 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1129 antibody.

In a further embodiment, the invention concerns screening assays toidentify agonists or antagonists of a native PRO1129 polypeptide.

In still a further embodiment, the invention concerns a compositioncomprising a PRO1129 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

77. PRO1068

A cDNA clone (DNA59214-1449) has been identified, that encodes a novelpolypeptide having homology to urotensin and designated the presentapplication as “PRO1068.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1068 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1068 polypeptide having the sequence of amino acidresidues from about 21 to about 124, inclusive of FIG. 184 (SEQ IDNO:266), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1068 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 102 and about413, inclusive, of FIG. 183 (SEQ ID NO:265). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203046(DNA59214-1449), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203046 (DNA59214-1449).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 21 to about 124, inclusive of FIG. 184 (SEQ IDNO:266), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least about 50 nucleotides, and preferably at leastabout 100 nucleotides and produced by hybridizing a test DNA moleculeunder stringent conditions with (a) a DNA molecule encoding a PRO1068polypeptide having the sequence of amino acid residues from about 21 toabout 124, inclusive of FIG. 184 (SEQ ID NO:266), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least aboutan 80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1068 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, or iscomplementary to such encoding nucleic acid molecule. The signal peptidehas been tentatively identified as extending from amino acid position 1through about amino acid position 20 in the sequence of FIG. 184 (SEQ IDNO:266).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 21to about 124, inclusive of FIG. 184 (SEQ ID NO:266), or (b) thecomplement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1068 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1068polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1068 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 21 to 124 of FIG. 184 (SEQ ID NO:266).

In another aspect, the invention concerns an isolated PRO1068polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues21 to about 124, inclusive of FIG. 184 (SEQ ID NO:266).

In a further aspect, the invention concerns an isolated PRO1068polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 21 to124 of FIG. 184 (SEQ ID NO:266).

In yet another aspect, the invention concerns an isolated PRO1068polypeptide, comprising the sequence of amino acid residues 21 to about124, inclusive of FIG. 184 (SEQ ID NO:266), or a fragment thereofsufficient to provide a binding site for an anti-PRO1068 antibody.Preferably, the PRO1068 fragment retains a qualitative biologicalactivity of a native PRO1068 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1068 polypeptide having the sequence ofamino acid residues from about 21 to about 124, inclusive of FIG. 184(SEQ ID NO:266), or (b) the complement of the DNA molecule of (a), andif the test DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1068 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1068 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1068 polypeptide, by contactingthe native PRO1068 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1068 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

78. PRO1066

Applicants have identified a cDNA clone (DNA59215-1425) that encodes anovel secreted polypeptide, designated in the present application as“PRO1066”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1066 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1066 polypeptide having the sequence of amino acidresidues from about 1 or about 24 to about 117, inclusive of FIG. 186(SEQ ID NO:268), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1066 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about nucleotides 176 orabout 245 and about 527, inclusive, of FIG. 185 (SEQ ID NO:267).Preferably, hybridization occurs under stringent hybridization and washconditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 209961(DNA59215-1425). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 209961 (DNA59215-1425).

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 24 to about 117, inclusive of FIG. 186 (SEQ IDNO:268).

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1066 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, or iscomplementary to such encoding nucleic acid molecule. The signal peptidehas been tentatively identified as extending from about amino acidposition 1 to about amino acid position 23 in the sequence of FIG. 186(SEQ ID NO:268).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA encoding a polypeptide scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 24 to about 117, inclusive of FIG. 186 (SEQ ID NO:268).

Another embodiment is directed to fragments of a PRO1066 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1066polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO1066 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 or about 24 to about 117 of FIG. 186 (SEQID NO:268).

In another aspect, the invention concerns an isolated PRO1066polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 24 to about 117, inclusive of FIG. 186 (SEQ ID NO:268).

In a further aspect, the invention concerns an isolated PRO1066polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 24 to about 117, inclusive of FIG. 186 (SEQ ID NO:268).

In yet another aspect, the invention concerns an isolated PRO1066polypeptide, comprising the sequence of amino acid residues 1 or about24 to about 117, inclusive of FIG. 186 (SEQ ID NO:268), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1066antibody. Preferably, the PRO1066 fragment retains a qualitativebiological activity of a native PRO1066 polypeptide.

In another aspect, the present invention is directed to fragments of aPRO1066 polypeptide which are sufficiently long to provide an epitopeagainst which an antibody may be generated.

79. PRO1184

Applicants have identified a cDNA clone (DNA59220-1514) that encodes anovel secreted polypeptide, designated in the present application as“PRO1184”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1184 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1184 polypeptide having the sequence of amino acidresidues from 1 or about 39 through 142 of FIG. 188 (SEQ ID NO:270), or(b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1184 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid at about residues 106 or 220 through531 of SEQ ID NO:269. In another aspect, the invention concerns anisolated nucleic acid molecule encoding a PRO1184 polypeptide comprisingDNA hybridizing to the complement of the nucleic of SEQ ID NO:269.Preferably, hybridization occurs under stringent hybridization and washconditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC of DNA59220-1514.In a preferred embodiment, the nucleic acid comprises a DNA encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit of DNA59220-1514.

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 39 through 142 of SEQ ID NO:270.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1184 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, and itssoluble variants, or is complementary to such an encoding nucleic acidmolecule. The signal peptide has been tentatively identified asextending from amino acid position 1 to about amino acid position 38 ofSEQ ID NO:270.

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA encoding a polypeptide scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 39 through 142 of SEQ ID NO:270.

Another embodiment is directed to fragments of a PRO1184 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1184polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO1184 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 or about 39 through 142 of SEQ ID NO:270.

In another aspect, the invention concerns an isolated PRO1184polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 39 through 142 of SEQ ID NO:270.

In a further aspect, the invention concerns an isolated PRO1184polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 39 through 142 of SEQ ID NO:270.

In yet another aspect, the invention concerns an isolated PRO1184polypeptide, comprising the sequence of amino acid residues 1 or about39 through 142 of SEQ ID NO:270, or a fragment thereof sufficient toprovide a binding site for an anti-PRO1184 antibody. Preferably, thePRO1184 fragment retains a qualitative biological activity of a nativePRO1184 polypeptide.

In another aspect, the present invention is directed to fragments of aPRO1184 polypeptide which are sufficiently long to provide an epitopeagainst which an antibody may be generated.

80. PRO1360

A cDNA clone (DNA59488-1603) has been identified that encodes a novelpolypeptide designated in the present application as “PRO1360.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1360 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1360 polypeptide having the sequence of amino acidresidues from about 30 to about 285, inclusive of FIG. 190 (SEQ IDNO:272), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1360 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 140 and about908, inclusive, of FIG. 189 (SEQ ID NO:271). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203157(DNA59488-1603), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203157 (DNA59488-1603).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 30 to about 285, inclusive of FIG. 190 (SEQ IDNO:272), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least about 50 nucleotides, and preferably at leastabout 100 nucleotides and produced by hybridizing a test DNA moleculeunder stringent conditions with (a) a DNA molecule encoding a PRO1360polypeptide having the sequence of amino acid residues from about 30 toabout 285, inclusive of FIG. 190 (SEQ ID NO:272), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least aboutan 80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 30to about 285, inclusive of FIG. 190 (SEQ ID NO:272), or (b) thecomplement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1360 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1360polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1360 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 30 through 285 of FIG. 190 (SEQ ID NO:272).

In another aspect, the invention concerns an isolated PRO1360polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues30 to about 285, inclusive of FIG. 190 (SEQ ID NO:272).

In a further aspect, the invention concerns an isolated PRO1360polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 30through 285 of FIG. 190 (SEQ ID NO:272).

In yet another aspect, the invention concerns an isolated PRO1360polypeptide, comprising the sequence of amino acid residues 30 to about285, inclusive of FIG. 190 (SEQ ID NO:272), or a fragment thereofsufficient to provide a binding site for an anti-PRO1360 antibody.Preferably, the PRO1360 fragment retains a qualitative biologicalactivity of a native PRO1360 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1360 polypeptide having the sequence ofamino acid residues from about 30 to about 285, inclusive of FIG. 190(SEQ ID NO:272), or (b) the complement of the DNA molecule of (a), andif the test DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1360 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1360 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1360 polypeptide, by contactingthe native PRO1360 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1360 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

81. PRO1029

A cDNA clone (DNA59493-1420) has been identified that encodes a novelsecreted polypeptide, designated in the present application as“PRO1029”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1029 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1029 polypeptide having the sequence of amino acidresidues from about 1 or about 20 to about 86, inclusive of FIG. 192(SEQ ID NO:274), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1029 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about nucleotides 39 or about96 and about 296, inclusive, of FIG. 191 (SEQ ID NO:274). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203050(DNA59493-1420) or (b) the complement of the nucleic acid molecule of(a). In a preferred embodiment, the nucleic acid comprises a DNAencoding the same mature polypeptide encoded by the human protein cDNAin ATCC Deposit No. 203050 (DNA59493-1420).

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 20 to about 86, inclusive of FIG. 192 (SEQ IDNO:274), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least 10 nucleotides and produced by hybridizing atest DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1029 polypeptide having the sequence of amino acidresidues from 1 or about 20 to about 86, inclusive of FIG. 192 (SEQ IDNO:274), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, preferably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1029 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, or iscomplementary to such encoding nucleic acid molecule. The signal peptidehas been tentatively identified as extending from about amino acidposition 1 to about amino acid position 19 in the sequence of FIG. 192(SEQ ID NO:274).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 20 to about 86, inclusive of FIG. 192 (SEQ ID NO:274), or (b)the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1029 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 191 (SEQ ID NO:273).

In another embodiment, the invention provides isolated PRO1029polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO1029 polypeptide, which in certain embodiments, includes an aminoacid sequence comprising residues 1 or about 20 to about 86 of FIG. 192(SEQ ID NO:274).

In another aspect, the invention concerns an isolated PRO1029polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 20 to about 86, inclusive of FIG. 192 (SEQ ID NO:274).

In a further aspect, the invention concerns an isolated PRO1029polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 20 to about 86, inclusive of FIG. 192 (SEQ ID NO:274).

In yet another aspect, the invention concerns an isolated PRO1029polypeptide, comprising the sequence of amino acid residues 1 or about20 to about 86, inclusive of FIG. 192 (SEQ ID NO:274), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1029antibody. Preferably, the PRO1029 fragment retains a qualitativebiological activity of a native PRO1029 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1029 polypeptide having the sequence ofamino acid residues from about 1 or about 20 to about 86, inclusive ofFIG. 192 (SEQ ID NO:274), or (b) the complement of the DNA molecule of(a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

82. PRO1139

Applicants have identified a novel cDNA clone (DNA59497-1496) thatencodes a novel human protein originally designated as PRO1139.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding a PRO1139 polypeptidehaving the sequence of amino acid residues from about 29 to about 131 ofFIG. 194 (SEQ ID NO:276), or (b) the complement of the DNA molecule of(a).

In another embodiment, the invention concerns an isolated nucleic acidmolecule comprising DNA hybridizing to the complement of thepolynucleotide sequence between about residues 80 and 391, inclusive, ofFIG. 193 (SEQ ID NO:275). Preferably, hybridization occurs understringent hybridization and wash conditions.

In a further embodiment, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 209941(DNA59497-1496). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 209941 (DNA59497-1496).

In a still further embodiment, the invention concerns an isolatednucleic acid molecule comprising DNA encoding a polypeptide having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 29 to about 131 of FIG. 194 (SEQ IDNO:276).

In a specific embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a native or variant PRO1139polypeptide, with or without the N-terminal signal sequence, and with orwithout the transmembrane regions which have been identified asstretching from about amino acid position 33 to about amino acidposition 52; from about amino acid position 71 to about amino acidposition 89; and from about amino acid position 98 to about amino acidposition 120, respectively of the amino acid sequence of FIG. 194, SEQID NO:276. In one aspect, the isolated nucleic acid comprises DNAencoding a mature, full-length native PRO1139 polypeptide having aminoacid residues 1 to 131 of FIG. 194, SEQ ID NO:276, or is complementaryto such encoding nucleic acid sequence.

In another embodiment, the invention concerns an isolated nucleic acidmolecule comprising DNA encoding a polypeptide scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues fromabout 29 to about 131 of FIG. 194 (SEQ ID NO:276).

In another embodiment, the invention provides isolated PRO1139polypeptides. In particular, the invention provides isolated nativesequence PRO1139 polypeptide, which in one embodiment, include the aminoacid sequence comprising residues 29 to 131 of FIG. 194 (SEQ ID NO:276).The invention also provides for variants of the PRO1139 polypeptidewhich are encoded by any of the isolated nucleic acid moleculeshereinabove defined. Specific variants include, but are not limited to,deletion (truncated) variants of the full-length native sequence PRO1139which lack the N-terminal signal sequence and/or have at least onetransmembrane domain deleted or inactivated. The variants specificallyinclude variants of the full-length mature polypeptide of FIG. 194 (SEQID NO:276) in which one or more of the transmembrane regions betweenamino acid residues 33–52, 71–8, and 98–120, respectively have beendeleted or inactivated, and which may additionally have the N-terminalsignal sequence (amino acid residues 1–28) and/or the initiatingmethionine deleted.

In a further embodiment, the invention concerns an isolated PRO1139polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues fromabout 29 to about 131 of FIG. 194 (SEQ ID NO:276).

In yet another aspect, the invention concerns an isolated PRO1139polypeptide, comprising the sequence of amino acid residues 29 to about131, inclusive of FIG. 194 (SEQ ID NO:276) or a fragment thereofsufficient to provide a binding site for an anti-PRO1139 antibody.Preferably, the PRO1139 fragment retains a qualitative biologicalactivity of a native PRO1139 polypeptide.

In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1139 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1139 antibody.

In a further embodiment, the invention concerns screening assays toidentify agonists or antagonists of a native PRO1139 polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1139 polypeptide (including variants), or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

The invention also concerns a method of treating obesity comprisingadministering to a patient an effective amount of an antagonist of aPRO1139 polypeptide. In a specific embodiment, the antagonist is ablocking antibody specifically binding a native PRO1139 polypeptide.

83. PRO1309

A cDNA clone (DNA59588-1571) has been identified that encodes a novelpolypeptide having leucine rich repeats and designated in the presentapplication as “PRO1309.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1309 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1309 polypeptide having the sequence of amino acidresidues from about 35 to about 522, inclusive of FIG. 196 (SEQ IDNO:278), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1309 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 822 and about2285, inclusive, of FIG. 195 (SEQ ID NO:277). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203106(DNA59588-1571), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203106 (DNA59588-1571).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 35 to about 522, inclusive of FIG. 196 (SEQ IDNO:278), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least about 50 nucleotides, and preferably at leastabout 100 nucleotides and produced by hybridizing a test DNA moleculeunder stringent conditions with (a) a DNA molecule encoding a PRO1309polypeptide having the sequence of amino acid residues from about 35 toabout 522, inclusive of FIG. 196 (SEQ ID NO:278), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least aboutan 80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1309 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, and itssoluble, i.e. transmembrane domain deleted or inactivated variants, oris complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from amino acidposition 1 through about amino acid position 34 in the sequence of FIG.196 (SEQ ID NO:278). The transmembrane domain has been tentativelyidentified as extending from about amino acid position 428 through aboutamino acid position 450 in the PRO1309 amino acid sequence (FIG. 196,SEQ ID NO:278).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 35to about 522, inclusive of FIG. 196 (SEQ ID NO:278), or (b) thecomplement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1309 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1309polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1309 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 35 through 522 of FIG. 196 (SEQ ID NO:278).

In another aspect, the invention concerns an isolated PRO1309polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues35 to about 522, inclusive of FIG. 196 (SEQ ID NO:278).

In a further aspect, the invention concerns an isolated PRO1309polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 35through 522 of FIG. 196 (SEQ ID NO:278).

In yet another aspect, the invention concerns an isolated PRO1309polypeptide, comprising the sequence of amino acid residues 35 to about522, inclusive of FIG. 196 (SEQ ID NO:278), or a fragment thereofsufficient to provide a binding site for an anti-PRO1309 antibody.Preferably, the PRO1309 fragment retains a qualitative biologicalactivity of a native PRO1309 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1309 polypeptide having the sequence ofamino acid residues from about 35 to about 522, inclusive of FIG. 196(SEQ ID NO:278), or (b) the complement of the DNA molecule of (a), andif the test DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1309 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1309 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1309 polypeptide, by contactingthe native PRO1309 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1309 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

84. PRO1028

Applicants have identified a cDNA clone that encodes a secreted novelpolypeptide, wherein the polypeptide is designated in the presentapplication as “PRO1028”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1028 polypeptide. In one aspect,the isolated nucleic acid comprises DNA encoding the PRO1028 polypeptidehaving amino acid residues 1 through 197 of FIG. 198 (SEQ ID NO:281), oris complementary to such encoding nucleic acid sequence, and remainsstably bound to it under at least moderate, and optionally, under highstringency conditions. The isolated nucleic acid sequence may comprisethe cDNA insert of the vector deposited on Jun. 9, 1998 with the ATCC asDNA59603-1419 which includes the nucleotide sequence encoding PRO1028.

In another embodiment, the invention provides isolated PRO1028polypeptide. In particular, the invention provides isolated nativesequence PRO1028 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 through 197 of FIG. 198 (SEQ IDNO:281). Optionally, the PRO1028 polypeptide is obtained or isobtainable by expressing the polypeptide encoded by the cDNA insert ofthe vector deposited on Jun. 9, 1998 with the ATCC as DNA59603-1419.

85. PRO1027

A cDNA clone (DNA59605-1418) has been identified, having a type IIfibronectin collagen-binding domain that encodes a novel polypeptide,designated in the present application as “PRO1027.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1027 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1027 polypeptide having the sequence of amino acidresidues from about 1 or 34 to about 77, inclusive of FIG. 200 (SEQ IDNO:283), or (b) the complement of the DNA molecule of (a). The term “or”as used herein to refer to amino or nucleic acids is meant to refer totwo alternative embodiments provided herein, i.e., 1–77, or in anotherembodiment, 34–77.

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1027 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 31 or 130 andabout 261, inclusive, of FIG. 199 (SEQ ID NO:282). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203005(DNA59605-1418), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203005 (DNA59605-1418).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 1 or 34 to about 77, inclusive of FIG. 200 (SEQID NO:283), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule produced by hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1027 polypeptide havingthe sequence of amino acid residues from about 1 or 34 to about 77,inclusive of FIG. 200 (SEQ ID NO:283), or (b) the complement of the DNAmolecule of (a), and, if the DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), isolating the testDNA molecule.

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 34 to about 77, inclusive of FIG. 200 (SEQ ID NO:283), or (b) thecomplement of the DNA of (a).

In another embodiment, the invention provides isolated PRO1027polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1027 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 or 34 through 77 of FIG. 200 (SEQ IDNO:283).

In another aspect, the invention concerns an isolated PRO1027polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 34 to about 77, inclusive of FIG. 200 (SEQ ID NO:283).

In a further aspect, the invention concerns an isolated PRO1027polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 34through 77 of FIG. 200 (SEQ ID NO:283).

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1027 polypeptide having the sequence ofamino acid residues from about 1 or 34 to about 77, inclusive of FIG.200 (SEQ ID NO:283), or (b) the complement of the DNA molecule of (a),and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1027 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1027 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1027 polypeptide, by contactingthe native PRO1027 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1027 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

86. PRO1107

Applicants have identified a cDNA clone that encodes a novel polypeptidehaving sequence identity with PC-1, wherein the polypeptide isdesignated in the present application as “PRO1107”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1107 polypeptide. In one aspect,the isolated nucleic acid comprises DNA encoding the PRO1107 polypeptidehaving amino acid residues 1 through 477 of FIG. 202 (SEQ ID NO:285), oris complementary to such encoding nucleic acid sequence, and remainsstably bound to it under at least moderate, and optionally, under highstringency conditions. In other aspects, the isolated nucleic acidcomprises DNA encoding the PRO1107 polypeptide having amino acidresidues about 23 through 477 of FIG. 202 (SEQ ID NO:285) or amino acidsabout 1 or 23 through 428±5 of FIG. 202 (SEQ ID NO:285), or iscomplementary to such encoding nucleic acid sequence, and remains stablybound to it under at least moderate, and optionally, under highstringency conditions. The isolated nucleic acid sequence may comprisethe cDNA insert of the DNA59606-1471 vector deposited on Jun. 9, 1998with the ATCC, which includes the nucleotide sequence encoding PRO1107.

In another embodiment, the invention provides isolated PRO1107polypeptide. In particular, the invention provides isolated nativesequence PRO1107 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 through 477 of FIG. 202 (SEQ IDNO:285). Additional embodiments of the present invention are directed toPRO1107 polypeptides comprising amino acids about 23 through 477 of FIG.202 (SEQ ID NO:285) or amino acids about 1 or 23 through 428±5 of FIG.202 (SEQ ID NO:285). Optionally, the PRO1107 polypeptide is obtained oris obtainable by expressing the polypeptide encoded by the cDNA insertof the DNA59606-1471 vector deposited with the ATCC on Jun. 9, 1998.

87. PRO1140

Applicants have identified a cDNA clone, DNA59607-1497, that encodes anovel multi-span transmembrane polypeptide wherein the polypeptide isdesignated in the present application as “PRO1140”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1140 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, and mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1140 polypeptide having the sequence of amino acidresidues from 1 to about 255, inclusive of FIG. 204 (SEQ ID NO:287), or(b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1140 polypeptide comprising DNA that hybridizesto the complement of the nucleic acid sequence having about residues 210to about 974, inclusive of FIG. 203 (SEQ ID NO:286). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, and most preferably at least about95% sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 209946(DNA59607-1497), which was deposited on Jun. 9, 1998, or (b) thecomplement of the DNA molecule of (a). In a preferred embodiment, thenucleic acid comprises a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 209946(DNA59607-1497).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, and mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 to about 255, inclusive of FIG. 204 (SEQ ID NO:287).

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1140 extracellular domain (ECD),with or without the initiating methionine, and its soluble variants(i.e. transmembrane domain(s) deleted or inactivated) or iscomplementary to such encoding nucleic acid molecule. Referring to thePRO1140 amino acid sequence (SEQ ID NO:287) shown in FIG. 204,transmembrane domain regions have been tentatively identified asextending from about amino acid positions 101 to about 118, about 141 toabout 161, and from about 172 to about 191.

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA encoding a polypeptide scoring at least about80% positives, preferably at least about 90% positives, and mostpreferably at least about 95% positives when compared with the aminoacid sequence of residues 1 to about 255, inclusive of FIG. 204 (SEQ IDNO:287).

Another embodiment is directed to fragments of a PRO1140 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1140polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO1140 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 to 255 of FIG. 204 (SEQ ID NO:287).

In another aspect, the invention concerns an isolated PRO1140polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, and most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 to 255, inclusive of FIG. 204 (SEQ ID NO:287).

In a further aspect, the invention concerns an isolated PRO1140polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, and most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 toabout 255 of FIG. 204 (SEQ ID NO:287).

In another aspect, the invention concerns a PRO1140 extracellular domaincomprising an amino acid sequence having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, and most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 to X of FIG. 204 (SEQ ID NO:287), wherein X is any one of amino acidresidues 96 to 105 of FIG. 204 (SEQ ID NO:287).

In yet another aspect, the invention concerns an isolated PRO1140polypeptide, comprising the sequence of amino acid residues 1 to about255, inclusive of FIG. 204 (SEQ ID NO:287), or a fragment thereofsufficient to provide a binding site for an anti-PRO1140 antibody.Preferably, the PRO1140 fragment retains a qualitative biologicalactivity of a native PRO1140 polypeptide.

In another aspect, the present invention is directed to fragments of aPRO1140 polypeptide which are sufficiently long to provide an epitopeagainst which an antibody may be generated.

88. PRO1106

Applicants have identified a cDNA clone that encodes a novel polypeptidehaving sequence identity with a peroxisomal calcium-dependent solutecarrier, wherein the polypeptide is designated in the presentapplication as “PRO1106”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1106 polypeptide. In one aspect,the isolated nucleic acid comprises DNA encoding the PRO1106 polypeptidehaving amino acid residues 1 through 469 of FIG. 206 (SEQ ID NO:289), oris complementary to such encoding nucleic acid sequence, and remainsstably bound to it under at least moderate, and optionally, under highstringency conditions. The isolated nucleic acid sequence may comprisethe cDNA insert of the DNA59609-1470 vector deposited on Jun. 9, 1998with the ATCC, which includes the nucleotide sequence encoding PRO1106.

In another embodiment, the invention provides isolated PRO1106polypeptide. In particular, the invention provides isolated nativesequence PRO1106 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 through 469 of FIG. 206 (SEQ IDNO:289). Optionally, the PRO1106 polypeptide is obtained or isobtainable by expressing the polypeptide encoded by the cDNA insert ofthe DNA59609-1470 vector deposited with the ATCC on Jun. 9, 1998.

89. PRO1291

A cDNA clone (DNA59610-1556) has been identified, having homology tonucleic acid encoding butyrophilin that encodes a novel polypeptide,designated in the present application as “PRO1291”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1291 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1291 polypeptide having the sequence of amino acidresidues from about 1 or about 29 to about 282, inclusive of FIG. 208(SEQ ID NO:291), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1291 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about nucleotides 61 or about145 and about 906, inclusive, of FIG. 207 (SEQ ID NO:290). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 209990(DNA59610-1556) or (b) the complement of the nucleic acid molecule of(a). In a preferred embodiment, the nucleic acid comprises a DNAencoding the same mature polypeptide encoded by the human protein cDNAin ATCC Deposit No. 209990 (DNA59610-1556).

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 29 to about 282, inclusive of FIG. 208 (SEQ IDNO:291), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least 10 nucleotides and produced by hybridizing atest DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1291 polypeptide having the sequence of amino acidresidues from 1 or about 29 to about 282, inclusive of FIG. 208 (SEQ IDNO:291), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, preferably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1291 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, and itssoluble, i.e., transmembrane domain deleted or inactivated variants, oris complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from about aminoacid position 1 to about amino acid position 28 in the sequence of FIG.208 (SEQ ID NO:291). The transmembrane domain has been tentativelyidentified as extending from about amino acid position 258 to aboutamino acid position 281 in the PRO1291 amino acid sequence (FIG. 208,SEQ ID NO:291).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 29 to about 282, inclusive of FIG. 208 (SEQ ID NO:291), or (b)the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1291 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 207 (SEQ ID NO:290).

In another embodiment, the invention provides isolated PRO1291polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO1291 polypeptide, which in certain embodiments, includes an aminoacid sequence comprising residues 1 or about 29 to about 282 of FIG. 208(SEQ ID NO:291).

In another aspect, the invention concerns an isolated PRO1291polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 29 to about 282, inclusive of FIG. 208 (SEQ ID NO:291).

In a further aspect, the invention concerns an isolated PRO1291polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 29 to about 282, inclusive of FIG. 208 (SEQ ID NO:291).

In yet another aspect, the invention concerns an isolated PRO1291polypeptide, comprising the sequence of amino acid residues 1 or about29 to about 282, inclusive of FIG. 208 (SEQ ID NO:291), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1291antibody. Preferably, the PRO1291 fragment retains a qualitativebiological activity of a native PRO1291 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1291 polypeptide having the sequence ofamino acid residues from about 1 or about 29 to about 282, inclusive ofFIG. 208 (SEQ ID NO:291), or (b) the complement of the DNA molecule of(a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1291 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1291 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1291 polypeptide by contactingthe native PRO1291 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1291 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

90. PRO1105

Applicants have identified a cDNA clone that encodes a novel polypeptidehaving two transmembrane domains, wherein the polypeptide is designatedin the present application as “PRO1105”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1105 polypeptide. In one aspect,the isolated nucleic acid comprises DNA encoding the PRO1105 polypeptidehaving amino acid residues 1 through 180 of FIG. 210 (SEQ ID NO:293), oris complementary to such encoding nucleic acid sequence, and remainsstably bound to it under at least moderate, and optionally, under highstringency conditions. In other aspects, the isolated nucleic acidcomprises DNA encoding the PRO1105 polypeptide having amino acidresidues about 20 through 180 of FIG. 210 (SEQ ID NO:293), or iscomplementary to such encoding nucleic acid sequence, and remains stablybound to it under at least moderate, and optionally, under highstringency conditions. The isolated nucleic acid sequence may comprisethe cDNA insert of the DNA59612-1466 vector deposited on Jun. 9, 1998with the ATCC, which includes the nucleotide sequence encoding PRO1105.

In another embodiment, the invention provides isolated PRO1105polypeptide. In particular, the invention provides isolated nativesequence PRO1105 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 through 180 of FIG. 210 (SEQ IDNO:293). Additional embodiments of the present invention are directed toPRO1105 polypeptides comprising amino acids about 20 through 180 of FIG.210 (SEQ ID NO:293). Other embodiments of the present invention aredirected to PRO1105 polypeptides comprising amino acids about 1 through79 and 100 through about 144 of FIG. 210 (SEQ ID NO:293). Optionally,the PRO1105 polypeptide is obtained or is obtainable by expressing thepolypeptide encoded by the cDNA insert of the DNA59612-1466 vectordeposited with the ATCC on Jun. 9, 1998.

91. PRO511

A cDNA clone (DNA59613-1417) has been identified, having some sequenceidentity with RoBo-1 and phospholipase inhibitors that encodes a novelpolypeptide, designated in the present application as “PRO1026.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1026 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1026 polypeptide having the sequence of amino acidresidues from about 1 or 26 to about 237, inclusive of FIG. 212 (SEQ IDNO:295), or (b) the complement of the DNA molecule of (a). The term “or”as used herein to refer to amino or nucleic acids is meant to refer totwo alternative embodiments provided herein, i.e., 1–237, or in anotherembodiment, 26–237.

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1026 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 233 or 308 andabout 943, inclusive, of FIG. 212 (SEQ ID NO:295). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203007(DNA59613-1417), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203007 (DNA59613-1417).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 1 or 26 to about 237, inclusive of FIG. 212(SEQ ID NO:295), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule produced by hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1026 polypeptide havingthe sequence of amino acid residues from about 1 or 26 to about 237,inclusive of FIG. 212 (SEQ ID NO:295), or (b) the complement of the DNAmolecule of (a), and, if the DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), isolating the testDNA molecule.

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 26 to about 237, inclusive of FIG. 212 (SEQ ID NO:295), or (b) thecomplement of the DNA of (a).

In another embodiment, the invention provides isolated PRO1026polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1026 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 or 26 through 237 of FIG. 212 (SEQ IDNO:295).

In another aspect, the invention concerns an isolated PRO1026polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 26 to about 237, inclusive of FIG. 212 (SEQ ID NO:295).

In a further aspect, the invention concerns an isolated PRO1026polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 26through 237 of FIG. 212 (SEQ ID NO:295).

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1026 polypeptide having the sequence ofamino acid residues from about 1 or 26 to about 237, inclusive of FIG.212 (SEQ ID NO:295), or (b) the complement of the DNA molecule of (a),and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1026 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1026 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1026 polypeptide, by contactingthe native PRO1026 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1026 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

92. PRO1104

A cDNA clone (DNA59616-1465) has been identified, that encodes a novelpolypeptide, designated in the present application as “PRO1104.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1104 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1104 polypeptide having the sequence of amino acidresidues from about 1 or about 23 to about 341, inclusive of FIG. 214(SEQ ID NO:297), or (b) the complement of the DNA molecule of (a). Theterm “or” as used herein to refer to amino or nucleic acids is meant torefer to two alternative embodiments provided herein, i.e., 1–341, or inanother embodiment, 23–341.

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1104 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 109 or 175 andabout 1131, inclusive, of FIG. 213 (SEQ ID NO:296). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 209991(DNA59616-1465), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.209991 (DNA59616-1465).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 1 or about 23 to about 341, inclusive of FIG.214 (SEQ ID NO:297), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule produced by hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1104 polypeptide havingthe sequence of amino acid residues from about 1 or about 23 to about341, inclusive of FIG. 214 (SEQ ID NO:297), or (b) the complement of theDNA molecule of (a), and, if the DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), isolating the testDNA molecule.

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 23 to about 341, inclusive of FIG. 214 (SEQ ID NO:297), or (b)the complement of the DNA of (a).

In another embodiment, the invention provides isolated PRO1104polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1104 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 or about 23 through 341 of FIG. 214 (SEQID NO:297).

In another aspect, the invention concerns an isolated PRO1104polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 23 through about 341, inclusive of FIG. 214 (SEQ ID NO:297).

In a further aspect, the invention concerns an isolated PRO1104polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 23 through 341 of FIG. 214 (SEQ ID NO:297).

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1104 polypeptide having the sequence ofamino acid residues from about 1 or about 23 to about 341, inclusive ofFIG. 214 (SEQ ID NO:297), or (b) the complement of the DNA molecule of(a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

93. PRO1100

A cDNA clone (DNA59619-1464) has been identified that encodes a novelpolypeptide having multiple transmembrane domains, designated in thepresent application as “PRO1100.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1100 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1100 polypeptide having the sequence of amino acidresidues from about 1 or 21 to about 320, inclusive of FIG. 216 (SEQ IDNO:299), or (b) the complement of the DNA molecule of (a). The term “or”as used herein to refer to amino or nucleic acids is meant to refer totwo alternative embodiments provided herein, i.e., 1–320, or in anotherembodiment, 21–320.

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1100 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 33 or 93 andabout 992, inclusive, of FIG. 215 (SEQ ID NO:298). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203041(DNA59619-1464), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203041 (DNA59619-1464).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 1 or 21 to about 320, inclusive of FIG. 216(SEQ ID NO:299), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule produced by hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1100 polypeptide havingthe sequence of amino acid residues from about 1 or 21 to about 320,inclusive of FIG. 216 (SEQ ID NO:299), or (b) the complement of the DNAmolecule of (a), and, if the DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), isolating the testDNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1100 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, and itssoluble, i.e. transmembrane domains deleted or inactivated variants, oris complementary to such encoding nucleic acid molecule.

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 21 to about 320, inclusive of FIG. 216 (SEQ ID NO:299), or (b) thecomplement of the DNA of (a).

In another embodiment, the invention provides isolated PRO1100polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1100 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 or 21 through 320 of FIG. 216 (SEQ IDNO:299).

In another aspect, the invention concerns an isolated PRO1100polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 21 to about 320, inclusive of FIG. 216 (SEQ ID NO:299).

In a further aspect, the invention concerns an isolated PRO1100polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 21through 320 of FIG. 216 (SEQ ID NO:299).

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1100 polypeptide having the sequence ofamino acid residues from about 1 or 21 to about 320, inclusive of FIG.216 (SEQ ID NO:299), or (b) the complement of the DNA molecule of (a),and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1100 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1100 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1100 polypeptide, by contactingthe native PRO1100 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1100 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

94. PRO836

A cDNA clone (DNA59620-1463) has been identified, having some sequenceidentity with SLS1 that encodes a novel polypeptide, designated in thepresent application as “PRO836.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO836 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO836 polypeptide having the sequence of amino acid residuesfrom about 1 or 30 to about 461, inclusive of FIG. 218 (SEQ ID NO:301),or (b) the complement of the DNA molecule of (a). The term “or” as usedherein to refer to amino or nucleic acids is meant to refer to twoalternative embodiments provided herein, i.e., 1–461, or in anotherembodiment, 30–461.

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO836 polypeptide comprising DNA hybridizing to thecomplement of the nucleic acid between about residues 65 or 152 andabout 1447, inclusive, of FIG. 217 (SEQ ID NO:300). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 209989(DNA59620-1463), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.209989 (DNA59620-1463).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 1 or 30 to about 461, inclusive of FIG. 218(SEQ ID NO:301), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule produced by hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO836 polypeptide havingthe sequence of amino acid residues from about 1 or 30 to about 461,inclusive of FIG. 218 (SEQ ID NO:301), or (b) the complement of the DNAmolecule of (a), and, if the DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), isolating the testDNA molecule.

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 30 to about 461, inclusive of FIG. 218 (SEQ ID NO:301), or (b) thecomplement of the DNA of (a).

In another embodiment, the invention provides isolated PRO836polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO836 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 or 30 through 461 of FIG. 218 (SEQ IDNO:301).

In another aspect, the invention concerns an isolated PRO836polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 30 to about 461, inclusive of FIG. 218 (SEQ ID NO:301).

In a further aspect, the invention concerns an isolated PRO836polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 30through 461 of FIG. 218 (SEQ ID NO:301).

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO836 polypeptide having the sequence ofamino acid residues from about 1 or 30 to about 461, inclusive of FIG.218 (SEQ ID NO:301), or (b) the complement of the DNA molecule of (a),and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO836 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO836 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO836 polypeptide, by contactingthe native PRO836 polypeptide with a candidate molecule and monitoring abiological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO836 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

95. PRO1141

A cDNA clone (DNA59625-1498) has been identified that encodes a noveltransmembrane polypeptide, designated in the present application as“PRO1141”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1141 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1141 polypeptide having the sequence of amino acidresidues from about 1 or about 20 to about 247, inclusive of FIG. 220(SEQ ID NO:303), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1141 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about nucleotides 204 orabout 261 and about 944, inclusive, of FIG. 219 (SEQ ID NO:302).Preferably, hybridization occurs under stringent hybridization and washconditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 209992(DNA59625-1498) or (b) the complement of the nucleic acid molecule of(a). In a preferred embodiment, the nucleic acid comprises a DNAencoding the same mature polypeptide encoded by the human protein cDNAin ATCC Deposit No. 209992 (DNA59625-1498).

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 20 to about 247, inclusive of FIG. 220 (SEQ IDNO:303), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least 10 nucleotides and produced by hybridizing atest DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1141 polypeptide having the sequence of amino acidresidues from 1 or about 20 to about 247, inclusive of FIG. 220 (SEQ IDNO:303), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, preferably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1141 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, and itssoluble, i.e., transmembrane domain deleted or inactivated variants, oris complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from about aminoacid position 1 to about amino acid position 19 in the sequence of FIG.220 (SEQ ID NO:303). The transmembrane domains have been tentativelyidentified as extending from about amino acid position 38 to about aminoacid position 57, from about amino acid position 67 to about amino acidposition 83, from about amino acid position 117 to about amino acidposition 139 and from about amino acid position 153 to about amino acidposition 170, in the PRO1141 amino acid sequence (FIG. 220, SEQ IDNO:303).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 20 to about 247, inclusive of FIG. 220 (SEQ ID NO:303), or (b)the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1141 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 219 (SEQ ID NO:302).

In another embodiment, the invention provides isolated PRO1141polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO1141 polypeptide, which in certain embodiments, includes an aminoacid sequence comprising residues 1 or about 20 to about 247 of FIG. 220(SEQ ID NO:303).

In another aspect, the invention concerns an isolated PRO1141polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 20 to about 247, inclusive of FIG. 220 (SEQ ID NO:303).

In a further aspect, the invention concerns an isolated PRO1141polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 20 to about 247, inclusive of FIG. 220 (SEQ ID NO:303).

In yet another aspect, the invention concerns an isolated PRO1141polypeptide, comprising the sequence of amino acid residues 1 or about20 to about 247, inclusive of FIG. 220 (SEQ ID NO:303), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1141antibody. Preferably, the PRO1141 fragment retains a qualitativebiological activity of a native PRO1141 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1141 polypeptide having the sequence ofamino acid residues from about 1 or about 20 to about 247, inclusive ofFIG. 220 (SEQ ID NO:303), or (b) the complement of the DNA molecule of(a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In another embodiment, the invention provides an expressed sequence tag(EST) designated herein as DNA33128 comprising the nucleotide sequenceof SEQ ID NO:304 (see FIG. 221).

In another embodiment, the invention provides an expressed sequence tag(EST) designated herein as DNA34256 comprising the nucleotide sequenceof SEQ ID NO:305 (see FIG. 222).

In another embodiment, the invention provides an expressed sequence tag(EST) designated herein as DNA47941 comprising the nucleotide sequenceof SEQ ID NO:306 (see FIG. 223).

In another embodiment, the invention provides an expressed sequence tag(EST) designated herein as DNA54389 comprising the nucleotide sequenceof SEQ ID NO:307 (see FIG. 224).

96. PRO1132

A cDNA clone (DNA59767-1489) has been identified that encodes a novelpolypeptide having sequence identity with serine proteases andtrypsinogen and designated in the present application as “PRO1132.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1132 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1132 polypeptide having the sequence of amino acidresidues from about 23 to about 293, inclusive of FIG. 226 (SEQ IDNO:309), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1132 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 420 and about1232, inclusive, of FIG. 225 (SEQ ID NO:308). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203108(DNA59767-1489), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203108 (DNA59767-1489).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 23 to about 293, inclusive of FIG. 226 (SEQ IDNO:309), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least about 50 nucleotides, and preferably at leastabout 100 nucleotides and produced by hybridizing a test DNA moleculeunder stringent conditions with (a) a DNA molecule encoding a PRO1132polypeptide having the sequence of amino acid residues from about 23 toabout 293, inclusive of FIG. 226 (SEQ ID NO:309), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least aboutan 80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 23to about 293, inclusive of FIG. 226 (SEQ ID NO:309), or (b) thecomplement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1132 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1132polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1132 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 23 through 293 of FIG. 226 (SEQ ID NO:309).

In another aspect, the invention concerns an isolated PRO1132polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues23 to about 293, inclusive of FIG. 226 (SEQ ID NO:309).

In a further aspect, the invention concerns an isolated PRO1132polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 23through 293 of FIG. 226 (SEQ ID NO:309).

In yet another aspect, the invention concerns an isolated PRO1132polypeptide, comprising the sequence of amino acid residues 23 to about293, inclusive of FIG. 226 (SEQ ID NO:309), or a fragment thereofsufficient to provide a binding site for an anti-PRO1132 antibody.Preferably, the PRO t132 fragment retains a qualitative biologicalactivity of a native PRO1132 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1132 polypeptide having the sequence ofamino acid residues from about 23 to about 293, inclusive of FIG. 226(SEQ ID NO:309), or (b) the complement of the DNA molecule of (a), andif the test DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1132 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1132 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1132 polypeptide, by contactingthe native PRO1132 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1132 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

97. PRO1346

A cDNA clone (DNA59776-1600) has been identified, that encodes a novelpolypeptide, designated in the present application as PRO1346 (or NL7),having homology to known TIE ligands.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding an NL7 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding an NL7 polypeptide having the sequence of amino acid residuesfrom about 51 to about 461, inclusive of FIG. 228 (SEQ ID NO:314), or(b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding an NL7 polypeptide comprising DNA hybridizing to thecomplement of the nucleic acid between about nucleotides 1–3 (ATG) andabout 1381–1383 (CGC, preceding the TAG stop codon), inclusive, of FIG.227 (SEQ ID NO:313). Preferably, hybridization occurs under stringenthybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203128(DNA59776-1600), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203128 (DNA59776-1600).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 51 to about 461, inclusive of FIG. 228 (SEQ IDNO:314), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least about 1000 nucleotides and produced byhybridizing a test DNA molecule under stringent conditions with (a) aDNA molecule encoding an NL7 polypeptide having the sequence of aminoacid residues from about 51 to about 461, inclusive of FIG. 228 (SEQ IDNO:314), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, preferably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding an NL7 polypeptide, with or without theinitiating methionine, or its soluble forms, i.e. transmembrane domaindeleted or inactivated variants, or is complementary to such encodingnucleic acid molecule. The transmembrane domain has been tentativelyidentified as extending from about amino acid position 31 to about aminoacid position 50 in the NL7 amino acid sequence (FIG. 228, SEQ IDNO:314).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 51to about 461, inclusive of FIG. 228 (SEQ ID NO:314), or (b) thecomplement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule, at least about 200 bases in length, which encodes a fragmentof a native NL7 polypeptide.

In another embodiment, the invention provides an isolated NL7polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides an isolated native sequenceNL7 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues from about 51 to about 461 of FIG. 228 (SEQID NO:314).

In another aspect, the invention concerns an isolated NL7 polypeptide,comprising an amino acid sequence having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residuesfrom about 51 to about 461, inclusive of FIG. 228 (SEQ ID NO:314).

In a further aspect, the invention concerns an isolated NL7 polypeptide,comprising an amino acid sequence scoring at least about 80% positives,preferably at least about 85% positives, more preferably at least about90% positives, most preferably at least about 95% positives whencompared with the amino acid sequence of residues 51 to 461 of FIG. 228(SEQ ID NO:314).

In yet another aspect, the invention concerns an isolated NL7polypeptide, comprising the sequence of amino acid residues from about51 to about 461, inclusive of FIG. 228 (SEQ ID NO:314), or a fragmentthereof sufficient to provide a binding site for an anti-NL7 antibody.Preferably, the NL7 fragment retains a qualitative biological activityof a native NL7 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding an NL7 polypeptide having the sequence ofamino acid residues from about 51 to about 461, inclusive of FIG. 228(SEQ ID NO:314), or (b) the complement of the DNA molecule of (a), andif the test DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of the a native NL7 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-NL7 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native NL7 polypeptide, by contacting thenative NL7 polypeptide with a candidate molecule and monitoring abiological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising an NL7 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

98. PRO1131

A cDNA clone (DNA59777-1480) has been identified that encodes a novelpolypeptide having sequence identity with LDL receptors and designatedin the present application as “PRO1131.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1131 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1131 polypeptide having the sequence of amino acidresidues from about 1 to about 280, inclusive of FIG. 230 (SEQ IDNO:319), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1131 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 144 and about983, inclusive, of FIG. 229 (SEQ ID NO:318). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203111(DNA59777-1480), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203111 (DNA59777-1480).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 1 to about 280, inclusive of FIG. 230 (SEQ IDNO:319), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least about 50 nucleotides, and preferably at leastabout 100 nucleotides and produced by hybridizing a test DNA moleculeunder stringent conditions with (a) a DNA molecule encoding a PRO1131polypeptide having the sequence of amino acid residues from about 1 toabout 280, inclusive of FIG. 230 (SEQ ID NO:319), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least aboutan 80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1131 polypeptide in its solubleform, i.e. transmembrane domain deleted or inactivated variants, or iscomplementary to such encoding nucleic acid molecule. The transmembranedomain (type II) has been tentatively identified as extending from aboutamino acid positions 49–74 in the amino acid sequence of FIG. 230, SEQID NO:319.

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1to about 280, inclusive of FIG. 230 (SEQ ID NO:319), or (b) thecomplement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1131 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1131polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1131 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 through 280 of FIG. 230 (SEQ ID NO:319).

In another aspect, the invention concerns an isolated PRO1131polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 to about 280, inclusive of FIG. 230 (SEQ ID NO:319).

In a further aspect, the invention concerns an isolated PRO1131polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1through 280 of FIG. 230 (SEQ ID NO:319).

In yet another aspect, the invention concerns an isolated PRO1131polypeptide, comprising the sequence of amino acid residues 1 to about280, inclusive of FIG. 230 (SEQ ID NO:319), or a fragment thereofsufficient to provide a binding site for an anti-PRO1131 antibody.Preferably, the PRO1131 fragment retains a qualitative biologicalactivity of a native PRO1131 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1131 polypeptide having the sequence ofamino acid residues from about 1 to about 280, inclusive of FIG. 230(SEQ ID NO:319), or (b) the complement of the DNA molecule of (a), andif the test DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1131 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1131 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1131 polypeptide, by contactingthe native PRO1131 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1131 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

In another embodiment, the invention provides an expressed sequence tag(EST) designated herein as DNA43546 comprising the nucleotide sequenceof FIG. 231 (SEQ ID NO:320).

99. PRO1281

A cDNA clone (DNA59820-1549) has been identified that encodes a novelsecreted polypeptide designated in the present application as “PRO1281”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1281 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1281 polypeptide having the sequence of amino acidresidues from about 16 to about 775, inclusive of FIG. 233 (SEQ IDNO:326), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1281 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 273 and about2552, inclusive, of FIG. 232 (SEQ ID NO:325). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203129(DNA59820-1549), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203129 (DNA59820-1549).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 16 to about 775, inclusive of FIG. 233 (SEQ IDNO:326), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least about 50 nucleotides, and preferably at leastabout 100 nucleotides and produced by hybridizing a test DNA moleculeunder stringent conditions with (a) a DNA molecule encoding a PRO1281polypeptide having the sequence of amino acid residues from about 16 toabout 775, inclusive of FIG. 233 (SEQ ID NO:326), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least aboutan 80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1281 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, or iscomplementary to such encoding nucleic acid molecule. The signal peptidehas been tentatively identified as extending from amino acid position 1through about amino acid position 15 in the sequence of FIG. 233 (SEQ IDNO:326).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 16to about 775, inclusive of FIG. 233 (SEQ ID NO:326), or (b) thecomplement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1281 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1281polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1281 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 16 to 775 of FIG. 233 (SEQ ID NO:326).

In another aspect, the invention concerns an isolated PRO1281polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues16 to about 775, inclusive of FIG. 233 (SEQ ID NO:326).

In a further aspect, the invention concerns an isolated PRO1281polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 16 to775 of FIG. 233 (SEQ ID NO:326).

In yet another aspect, the invention concerns an isolated PRO1281polypeptide, comprising the sequence of amino acid residues 16 to about775, inclusive of FIG. 233 (SEQ ID NO:326), or a fragment thereofsufficient to provide a binding site for an anti-PRO1281 antibody.Preferably, the PRO1281 fragment retains a qualitative biologicalactivity of a native PRO1281 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1281 polypeptide having the sequence ofamino acid residues from about 16 to about 775, inclusive of FIG. 233(SEQ ID NO:326), or (b) the complement of the DNA molecule of (a), andif the test DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

100. PRO1064

A cDNA clone (DNA59827-1426) has been identified that encodes a noveltransmembrane polypeptide, designated in the present application as“PRO1064”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1064 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1064 polypeptide having the sequence of amino acidresidues from about 1 or about 25 to about 153, inclusive of FIG. 235(SEQ ID NO:334), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1064 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about nucleotides 532 orabout 604 and about 990, inclusive, of FIG. 234 (SEQ ID NO:333).Preferably, hybridization occurs under stringent hybridization and washconditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203089(DNA59827-1426) or (b) the complement of the nucleic acid molecule of(a). In a preferred embodiment, the nucleic acid comprises a DNAencoding the same mature polypeptide encoded by the human protein cDNAin ATCC Deposit No. 203089 (DNA59827-1426).

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 25 to about 153, inclusive of FIG. 235 (SEQ IDNO:334), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least 10 nucleotides and produced by hybridizing atest DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1064 polypeptide having the sequence of amino acidresidues from 1 or about 25 to about 153, inclusive of FIG. 235 (SEQ IDNO:334), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, preferably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1064 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, and itssoluble, i.e., transmembrane domain deleted or inactivated variants, oris complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from about aminoacid position 1 to about amino acid position 24 in the sequence of FIG.235 (SEQ ID NO:334). The transmembrane domain has been tentativelyidentified as extending from about amino acid position 89 to about aminoacid position 110 in the PRO1064 amino acid sequence (FIG. 235, SEQ IDNO:334).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 25 to about 153, inclusive of FIG. 235 (SEQ ID NO:334), or (b)the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1064 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 234 (SEQ ID NO:333).

In another embodiment, the invention provides isolated PRO1064polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO1064 polypeptide, which in certain embodiments, includes an aminoacid sequence comprising residues 1 or about 25 to about 153 of FIG. 235(SEQ ID NO:334).

In another aspect, the invention concerns an isolated PRO1064polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 25 to about 153, inclusive of FIG. 235 (SEQ ID NO:334).

In a further aspect, the invention concerns an isolated PRO1064polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 25 to about 153, inclusive of FIG. 235 (SEQ ID NO:334).

In yet another aspect, the invention concerns an isolated PRO1064polypeptide, comprising the sequence of amino acid residues 1 or about25 to about 153, inclusive of FIG. 235 (SEQ ID NO:334), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1064antibody. Preferably, the PRO1064 fragment retains a qualitativebiological activity of a native PRO1064 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1064 polypeptide having the sequence ofamino acid residues from about 1 or about 25 to about 153, inclusive ofFIG. 235 (SEQ ID NO:334), or (b) the complement of the DNA molecule of(a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In another embodiment, the invention provides an expressed sequence tag(EST) designated herein as DNA45288 comprising the nucleotide sequenceof SEQ ID NO:335 (see FIG. 236).

101. PRO1379

A cDNA clone (DNA59828-1608) has been identified that encodes a novelsecreted polypeptide designated in the present application as “PRO1379.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1379 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1379 polypeptide having the sequence of amino acidresidues from about 18 to about 574, inclusive of FIG. 238 (SEQ IDNO:340), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1379 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 61 and about1731, inclusive, of FIG. 237 (SEQ ID NO:339). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203158(DNA59828-1608), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203158 (DNA59828-1608).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 18 to about 574, inclusive of FIG. 238 (SEQ IDNO:340), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least about 50 nucleotides, and preferably at leastabout 100 nucleotides and produced by hybridizing a test DNA moleculeunder stringent conditions with (a) a DNA molecule encoding a PRO1379polypeptide having the sequence of amino acid residues from about 18 toabout 574, inclusive of FIG. 238 (SEQ ID NO:340), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least aboutan 80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1379 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, or iscomplementary to such encoding nucleic acid molecule. The signal peptidehas been tentatively identified as extending from amino acid position 1through about amino acid position 17 in the sequence of FIG. 238 (SEQ IDNO:340).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 18to about 574, inclusive of FIG. 238 (SEQ ID NO:340), or (b) thecomplement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1379 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1379polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1379 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 18 to 574 of FIG. 238 (SEQ ID NO:340).

In another aspect, the invention concerns an isolated PRO1379polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues18 to about 574, inclusive of FIG. 238 (SEQ ID NO:340).

In a further aspect, the invention concerns an isolated PRO1379polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 18 to574 of FIG. 238 (SEQ ID NO:340).

In yet another aspect, the invention concerns an isolated PRO1379polypeptide, comprising the sequence of amino acid residues 18 to about574, inclusive of FIG. 238 (SEQ ID NO:340), or a fragment thereofsufficient to provide a binding site for an anti-PRO1379 antibody.Preferably, the PRO1379 fragment retains a qualitative biologicalactivity of a native PRO1379 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1379 polypeptide having the sequence ofamino acid residues from about 18 to about 574, inclusive of FIG. 238(SEQ ID NO:340), or (b) the complement of the DNA molecule of (a), andif the test DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

102. PRO844

A cDNA clone (DNA59838-1462) has been identified, having sequenceidentity with protease inhibitors, that encodes a novel polypeptide,designated in the present application as “PRO844.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO844 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO844 polypeptide having the sequence of amino acid residuesfrom about 1 or 20 to about 111, inclusive of FIG. 240 (SEQ ID NO:345),or (b) the complement of the DNA molecule of (a). The term “or” as usedherein to refer to amino or nucleic acids is meant to refer to twoalternative embodiments provided herein, i.e., 1–111, or in anotherembodiment, 20–111.

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO844 polypeptide comprising DNA hybridizing to thecomplement of the nucleic acid between about residues 5 or 62 and about337, inclusive, of FIG. 239 (SEQ ID NO:344). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 209976(DNA59838-1462), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.209976 (DNA59838-1462).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 1 or 20 to about 111, inclusive of FIG. 240(SEQ ID NO:345), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule produced by hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO844 polypeptide havingthe sequence of amino acid residues from about 1 or 20 to about 111,inclusive of FIG. 240 (SEQ ID NO:345), or (b) the complement of the DNAmolecule of (a), and, if the DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), isolating the testDNA molecule.

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 20 to about 111, inclusive of FIG. 240 (SEQ ID NO:345), or (b) thecomplement of the DNA of (a).

In another embodiment, the invention provides isolated PRO844polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO844 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 or 20 through 111 of FIG. 240 (SEQ IDNO:345).

In another aspect, the invention concerns an isolated PRO844polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 20 to about 111, inclusive of FIG. 240 (SEQ ID NO:345).

In a further aspect, the invention concerns an isolated PRO844polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 20through 111 of FIG. 240 (SEQ ID NO:345).

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO844 polypeptide having the sequence ofamino acid residues from about 1 or 20 to about 111, inclusive of FIG.240 (SEQ ID NO:345), or (b) the complement of the DNA molecule of (a),and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO844 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO844 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO844 polypeptide, by contactingthe native PRO844 polypeptide with a candidate molecule and monitoring abiological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO844 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

103. PRO848

A cDNA clone (DNA59839-1461) has been identified, having sequenceidentity with sialytransferases that encodes a novel polypeptide,designated in the present application as “PRO848.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO848 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO848 polypeptide having the sequence of amino acid residuesfrom about 1 or 36 to about 600, inclusive of FIG. 242 (SEQ ID NO:347),or (b) the complement of the DNA molecule of (a). The term “or” as usedherein to refer to amino or nucleic acids is meant to refer to twoalternative embodiments provided herein, i.e., 1–600, or in anotherembodiment, 36–600.

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO848 polypeptide comprising DNA hybridizing to thecomplement of the nucleic acid between about residues 1 or 251 and about1945, inclusive, of FIG. 241 (SEQ ID NO:346). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 209988(DNA59839-1461), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.209988 (DNA59839-1461).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 1 or 36 to about 600, inclusive of FIG. 242(SEQ ID NO:347), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule produced by hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO848 polypeptide havingthe sequence of amino acid residues from about 1 or 36 to about 600,inclusive of FIG. 242 (SEQ ID NO:347), or (b) the complement of the DNAmolecule of (a), and, if the DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), isolating the testDNA molecule.

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 36 to about 600, inclusive of FIG. 242 (SEQ ID NO:347), or (b) thecomplement of the DNA of (a).

In another embodiment, the invention provides isolated PRO848polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO848 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 or 36 through 600 of FIG. 242 (SEQ IDNO:347).

In another aspect, the invention concerns an isolated PRO848polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 36 to about 600, inclusive of FIG. 242 (SEQ ID NO:347).

In a further aspect, the invention concerns an isolated PRO848polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 36through 600 of FIG. 242 (SEQ ID NO:347).

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO848 polypeptide having the sequence ofamino acid residues from about 1 or 36 to about 600, inclusive of FIG.242 (SEQ ID NO:347), or (b) the complement of the DNA molecule of (a),and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO848 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO848 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO848 polypeptide, by contactingthe native PRO848 polypeptide with a candidate molecule and monitoring abiological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO848 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

104. PRO1097

Applicants have identified a cDNA clone (DNA59841-1460) that encodes anovel secreted polypeptide having domains therein from the glycoproteasefamily proteins and the acyltransferase ChoActase/COT/CPT family,wherein the polypeptide is designated in the present application as“PRO1097”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1097 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1097 polypeptide having the sequence of amino acidresidues from about 1 or 21 to about 91, inclusive of FIG. 244 (SEQ IDNO:349), or (b) the complement of the DNA molecule of (a). The term “or”as used herein to refer to amino or nucleic acids is meant to refer totwo alternative embodiments provided herein, i.e., 1–91, or in anotherembodiment, 21–91.

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1097 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 3 or 63 andabout 275, inclusive, of FIG. 243 (SEQ ID NO:348). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203044(DNA59841-1460), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203044 (DNA59841-1460).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 1 or 21 to about 91, inclusive of FIG. 244 (SEQID NO:349), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule produced by hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1097 polypeptide havingthe sequence of amino acid residues from about 1 or 21 to about 91,inclusive of FIG. 244 (SEQ ID NO:349), or (b) the complement of the DNAmolecule of (a), and, if the DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), isolating the testDNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1097 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine. Thesignal peptide has been tentatively identified as extending from aminoacid position 1 through about amino acid position 20 in the sequence ofFIG. 244 (SEQ ID NO:349).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 21 to about 91, inclusive of FIG. 244 (SEQ ID NO:349), or (b) thecomplement of the DNA of (a).

In another embodiment, the invention provides isolated PRO1097polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1097 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 or 21 through 91 of FIG. 244 (SEQ IDNO:349).

In another aspect, the invention concerns an isolated PRO1097polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 21 to about 91, inclusive of FIG. 244 (SEQ ID NO:349).

In a further aspect, the invention concerns an isolated PRO1097polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 21through 91 of FIG. 244 (SEQ ID NO:349).

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1097 polypeptide having the sequence ofamino acid residues from about 1 or 21 to about 91, inclusive of FIG.244 (SEQ ID NO:349), or (b) the complement of the DNA molecule of (a),and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1097 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1097 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1097 polypeptide, by contactingthe native PRO1097 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1097 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

105. PRO1153

A cDNA clone (DNA59842-1502) has been identified, having twotransmembrane domains and being very proline rich, that encodes a novelpolypeptide, designated in the present application as “PRO1153.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1153 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1153 polypeptide having the sequence of amino acidresidues from about 1 to about 197, inclusive of FIG. 246 (SEQ IDNO:351), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1153 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 92 and about682, inclusive, of FIG. 245 (SEQ ID NO:350). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 209982(DNA59842-1502), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.209982 (DNA59842-1502).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 1 to about 197, inclusive of FIG. 246 (SEQ IDNO:351), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule produced by hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1153 polypeptide havingthe sequence of amino acid residues from about 1 to about 197, inclusiveof FIG. 246 (SEQ ID NO:351), or (b) the complement of the DNA moleculeof (a), and, if the DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), isolating the testDNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1153 polypeptide, and its soluble,i.e. transmembrane domain deleted or inactivated variants, or iscomplementary to such encoding nucleic acid molecule. The transmembranedomains have been tentatively identified as extending from about aminoacid positions 10–28 and 85–110 in the PRO1153 amino acid sequence (FIG.246, SEQ ID NO:351).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1to about 197, inclusive of FIG. 246 (SEQ ID NO:351), or (b) thecomplement of the DNA of (a).

In another embodiment, the invention provides isolated PRO1153polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1153 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 to 197 of FIG. 246 (SEQ ID NO:351).

In another aspect, the invention concerns an isolated PRO1153polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 to about 197, inclusive of FIG. 246 (SEQ ID NO:351).

In a further aspect, the invention concerns an isolated PRO1153polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1through 197 of FIG. 246 (SEQ ID NO:351).

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1153 polypeptide having the sequence ofamino acid residues from about 1 to about 197, inclusive of FIG. 246(SEQ ID NO:351), or (b) the complement of the DNA molecule of (a), andif the test DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

106. PRO1154

A cDNA clone (DNA59846-1503) has been identified that encodes a novelaminopeptidase, designated in the present application as “PRO1154.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1154 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1154 polypeptide having the sequence of amino acidresidues from about 1 or 35 to about 941, inclusive of FIG. 248 (SEQ IDNO:353), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1154 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 86 or 188 andabout 2908, inclusive, of FIG. 247 (SEQ ID NO:35 2). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 209978(DNA59846-1503), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.209978 (DNA59846-1503).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 1 or 35 to about 941, inclusive of FIG. 248(SEQ ID NO:353), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule produced by hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1154 polypeptide havingthe sequence of amino acid residues from about 1 or 35 to about 941,inclusive of FIG. 258 (SEQ ID NO:353), or (b) the complement of the DNAmolecule of (a), and, if the DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), isolating the testDNA molecule.

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 35 to about 941, inclusive of FIG. 248 (SEQ ID NO:353), or (b) thecomplement of the DNA of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule consisting essentially of DNA encoding a polypeptide havingamino acids 1 or 35 through about 73 of SEQ ID NO:353.

In another embodiment, the invention provides isolated PRO1154polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1154 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 or 35 to 941 of FIG. 248 (SEQ ID NO:353).

In a specific aspect, the invention provides a polypeptide having aminoacids 1 or 35 through about 73 of SEQ ID NO:353.

In another aspect, the invention concerns an isolated PRO1154polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 35 to about 941, inclusive of FIG. 248 (SEQ ID NO:353).

In a further aspect, the invention concerns an isolated PRO1154polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 35through 941 of FIG. 248 (SEQ ID NO:353).

In yet another aspect, the invention concerns an isolated PRO1154polypeptide, comprising the sequence of amino acid residues 1 or 35 toabout 941, inclusive of FIG. 248 (SEQ ID NO:353), or a fragment thereofsufficient to provide a binding site for an anti-PRO1154 antibody.Preferably, the PRO1154 fragment retains a qualitative biologicalactivity of a native PRO1154 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1154 polypeptide having the sequence ofamino acid residues from about 1 or 35 to about 941, inclusive of FIG.248 (SEQ ID NO:353), or (b) the complement of the DNA molecule of (a),and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1154 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1154 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1154 polypeptide, by contactingthe native PRO1154 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1154 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

107. PRO1181

A cDNA clone (DNA59847-1511) has been identified that encodes a novelsecreted polypeptide, designated in the present application as“PRO1181”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1181 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1181 polypeptide having the sequence of amino acidresidues from about 1 or about 16 to about 437, inclusive of FIG. 250(SEQ ID NO:355), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1181 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about nucleotides 17 or about62 and about 1327, inclusive, of FIG. 249 (SEQ ID NO:354). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203098(DNA59847-1511) or (b) the complement of the nucleic acid molecule of(a). In a preferred embodiment, the nucleic acid comprises a DNAencoding the same mature polypeptide encoded by the human protein cDNAin ATCC Deposit No. 203098 (DNA59847-1511).

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 16 to about 437, inclusive of FIG. 250 (SEQ IDNO:355), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least 10 nucleotides and produced by hybridizing atest DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1181 polypeptide having the sequence of amino acidresidues from 1 or about 16 to about 437, inclusive of FIG. 250 (SEQ IDNO:355), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, preferably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1181 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine or iscomplementary to such encoding nucleic acid molecule. The signal peptidehas been tentatively identified as extending from about amino acidposition 1 to about amino acid position 15 in the sequence of FIG. 250(SEQ ID NO:355). The transmembrane domain is at amino acids positions243–260 of FIG. 250.

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 16 to about 437, inclusive of FIG. 250 (SEQ ID NO:355), or (b)the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1181 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 249 (SEQ ID NO:354).

In another embodiment, the invention provides isolated PRO1181polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO1181 polypeptide, which in certain embodiments, includes an aminoacid sequence comprising residues 1 or about 16 to about 437 of FIG. 250(SEQ ID NO:355).

In another aspect, the invention concerns an isolated PRO1181polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 16 to about 437, inclusive of FIG. 250 (SEQ ID NO:355).

In a further aspect, the invention concerns an isolated PRO1181polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 16 to about 437, inclusive of FIG. 250 (SEQ ID NO:355).

In yet another aspect, the invention concerns an isolated PRO1181polypeptide, comprising the sequence of amino acid residues 1 or about16 to about 437, inclusive of FIG. 250 (SEQ ID NO:355), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1181antibody. Preferably, the PRO1181 fragment retains a qualitativebiological activity of a native PRO1181 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1181 polypeptide having the sequence ofamino acid residues from about 1 or about 16 to about 437, inclusive ofFIG. 250 (SEQ ID NO:355), or (b) the complement of the DNA molecule of(a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

108. PRO1182

A cDNA clone (DNA59848-1512) has been identified, having homology tonucleic acid encoding conglutinin that encodes a novel polypeptide,designated in the present application as “PRO1182”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1182 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1182 polypeptide having the sequence of amino acidresidues from about 1 or about 26 to about 271, inclusive of FIG. 252(SEQ ID NO:357), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1182 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about nucleotides 67 or about142 and about 879, inclusive, of FIG. 251 (SEQ ID NO:356). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203088(DNA59848-1512) or (b) the complement of the nucleic acid molecule of(a). In a preferred embodiment, the nucleic acid comprises a DNAencoding the same mature polypeptide encoded by the human protein cDNAin ATCC Deposit No. 203088 (DNA59848-1512).

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 26 to about 271, inclusive of FIG. 252 (SEQ IDNO:357), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least 10 nucleotides and produced by hybridizing atest DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1182 polypeptide having the sequence of amino acidresidues from 1 or about 26 to about 271, inclusive of FIG. 252 (SEQ IDNO:357), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, preferably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1182 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine or iscomplementary to such encoding nucleic acid molecule. The signal peptidehas been tentatively identified as extending from about amino acidposition 1 to about amino acid position 25 in the sequence of FIG. 252(SEQ ID NO:357).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 26 to about 271, inclusive of FIG. 252 (SEQ ID NO:357), or (b)the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1182 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 251 (SEQ ID NO:356).

In another embodiment, the invention provides isolated PRO1182polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO1182 polypeptide, which in certain embodiments, includes an aminoacid sequence comprising residues 1 or about 26 to about 271 of FIG. 252(SEQ ID NO:357).

In another aspect, the invention concerns an isolated PRO1182polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 26 to about 271, inclusive of FIG. 252 (SEQ ID NO:357).

In a further aspect, the invention concerns an isolated PRO1182polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 26 to about 271, inclusive of FIG. 252 (SEQ ID NO:357).

In yet another aspect, the invention concerns an isolated PRO1182polypeptide, comprising the sequence of amino acid residues 1 or about26 to about 271, inclusive of FIG. 252 (SEQ ID NO:357), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1182antibody. Preferably, the PRO1182 fragment retains a qualitativebiological activity of a native PRO1182 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1182 polypeptide having the sequence ofamino acid residues from about 1 or about 26 to about 271, inclusive ofFIG. 252 (SEQ ID NO:357), or (b) the complement of the DNA molecule of(a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1182 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1182 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1182 polypeptide by contactingthe native PRO1182 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1182 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

109. PRO1155

A cDNA clone (DNA59849-1504) has been identified, having sequenceidentity with neurokinin B that encodes a novel polypeptide, designatedin the present application as “PRO1155.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1155 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1155 polypeptide having the sequence of amino acidresidues from about 1 or 19 to about 135, inclusive of FIG. 254 (SEQ IDNO:359), or (b) the complement of the DNA molecule of (a). The term “or”as used herein to refer to nucleic or amino acids is meant to conveyalternative embodiments, i.e., 1–135 or alternatively in anotherembodiment, 19–135.

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1155 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 158 or 212 andabout 562, inclusive, of FIG. 253 (SEQ ID NO:358). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 209986(DNA59849-1504), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.209986 (DNA59849-1504).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 1 or 19 to about 135, inclusive of FIG. 254(SEQ ID NO:359), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule produced by hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1155 polypeptide havingthe sequence of amino acid residues from about 19 to about 135,inclusive of FIG. 254 (SEQ ID NO:359), or (b) the complement of the DNAmolecule of (a), and, if the DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), isolating the testDNA molecule.

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 19 to about 135, inclusive of FIG. 254 (SEQ ID NO:359), or (b) thecomplement of the DNA of (a).

In another embodiment, the invention provides isolated PRO1155polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1155 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 or 19 through 135 of FIG. 254 (SEQ IDNO:359).

In another aspect, the invention concerns an isolated PRO1155polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 19 to about 135, inclusive of FIG. 254 (SEQ ID NO:359).

In a further aspect, the invention concerns an isolated PRO1155polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 19through 135 of FIG. 254 (SEQ ID NO:359).

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1155 polypeptide having the sequence ofamino acid residues from about 1 or 19 to about 135, inclusive of FIG.254 (SEQ ID NO:359), or (b) the complement of the DNA molecule of (a),and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1155 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1155 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1155 polypeptide, by contactingthe native PRO1155 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1155 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

110. PRO1156

A cDNA clone (DNA59853-1505) has been identified that encodes a novelsecreted polypeptide, designated in the present application as“PRO1156.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1156 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1156 polypeptide having the sequence of amino acidresidues from about 23 to about 159, inclusive of FIG. 256 (SEQ IDNO:361), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1156 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 281 and about688, inclusive, of FIG. 255 (SEQ ID NO:360). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 209985(DNA59853-1505), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.209985 (DNA59853-1505).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 23 to about 159, inclusive of FIG. 256 (SEQ IDNO:361), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least 50 nucleotides, preferably at least 100nucleotides, and produced by hybridizing a test DNA molecule understringent conditions with (a) a DNA molecule encoding a PRO1156polypeptide having the sequence of amino acid residues from about 23 toabout 159, inclusive of FIG. 256 (SEQ ID NO:361), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least aboutan 80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1156 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, or iscomplementary to such encoding nucleic acid molecule. The signal peptidehas been tentatively identified as extending from amino acid position 1to about amino acid position 22 in the sequence of FIG. 256 (SEQ IDNO:361).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 23to about 159, inclusive of FIG. 256 (SEQ ID NO:361), or (b) thecomplement of the DNA of (a).

In another aspect, the invention concerns hybridization probes thatcomprise fragments of the PRO784 coding sequence, or complementarysequence thereof. The hybridization probes preferably have at leastabout 20 nucleotides to about 80 nucleotides, and more preferably, atleast about 20 to about 50 nucleotides.

In another embodiment, the invention provides isolated PRO1156polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1156 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 23 to 159 of FIG. 256 (SEQ ID NO:361).

In another aspect, the invention concerns an isolated PRO1156polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues23 to about 159, inclusive of FIG. 256 (SEQ ID NO:361).

In a further aspect, the invention concerns an isolated PRO1156polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 23 to159 of FIG. 256 (SEQ ID NO:361).

In yet another aspect, the invention concerns an isolated PRO1156polypeptide, comprising the sequence of amino acid residues 23 to about159, inclusive of FIG. 256 (SEQ ID NO:361), or a fragment thereofsufficient to provide a binding site for an anti-PRO1156 antibody.Preferably, the PRO1156 fragment retains a qualitative biologicalactivity of a native PRO1156 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1156 polypeptide having the sequence ofamino acid residues from about 23 to about 159, inclusive of FIG. 256(SEQ ID NO:361), or (b) the complement of the DNA molecule of (a), andif the test DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

111. PRO1098

A cDNA clone (DNA59854-1459) has been identified which encodes a novelpolypeptide, designated in the present application as “PRO1098.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1098 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1098 polypeptide having the sequence of amino acidresidues from about 1 or 20 to about 78, inclusive of FIG. 258 (SEQ IDNO:363), or (b) the complement of the DNA molecule of (a). The term “or”as used herein to refer to amino or nucleic acids is meant to refer totwo alternative embodiments provided herein, i.e., 1–78, or in anotherembodiment, 20–78.

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1098 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 58 or 115 andabout 291, inclusive, of FIG. 257 (SEQ ID NO:362). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 851% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 209974(DNA59854-1459), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.209974 (DNA59854-1459).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 1 or 20 to about 78, inclusive of FIG. 258 (SEQID NO:363), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule produced by hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1098 polypeptide havingthe sequence of amino acid residues from about 1 or 20 to about 78,inclusive of FIG. 258 (SEQ ID NO:363), or (b) the complement of the DNAmolecule of (a), and, if the DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), isolating the testDNA molecule.

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 20 to about 78, inclusive of FIG. 258 (SEQ ID NO:363), or (b) thecomplement of the DNA of (a).

In another embodiment, the invention provides isolated PRO1098polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1098 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 or 20 through 78 of FIG. 258 (SEQ IDNO:363).

In another aspect, the invention concerns an isolated PRO1098polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 20 to about 78, inclusive of FIG. 258 (SEQ ID NO:363).

In a further aspect, the invention concerns an isolated PRO1098polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 20through 78 of FIG. 258 (SEQ ID NO:363).

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1098 polypeptide having the sequence ofamino acid residues from about 1 or 20 to about 78, inclusive of FIG.258 (SEQ ID NO:363), or (b) the complement of the DNA molecule of (a),and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

112. PRO1127

A cDNA clone (DNA60283-1484) has been identified that encodes a novelsecreted polypeptide, designated in the present application as“PRO1127.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1127 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1127 polypeptide having the sequence of amino acidresidues from about 1 or 30 to about 67, inclusive of FIG. 260 (SEQ IDNO:365), or (b) the complement of the DNA molecule of (a). The term “or”in reference to amino or nucleic acids as used herein refers to twoalternative embodiments, i.e., 1–67 in one embodiment, or alternatively,30–67.

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1127 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 126 or 213 andabout 326, inclusive, of FIG. 259 (SEQ ID NO:364). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203043(DNA60283-1484), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203043 (DNA60283-1484).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 1 or 30 to about 67, inclusive of FIG. 260 (SEQID NO:365), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule produced by hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1127 polypeptide havingthe sequence of amino acid residues from about 1 or 30 to about 67,inclusive of FIG. 260 (SEQ ID NO:365), or (b) the complement of the DNAmolecule of (a), and, if the DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), isolating the testDNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1127polypeptide without theN-terminal signal sequence and/or the initiating methionine. The signalpeptide has been tentatively identified as extending from amino acidposition 1 through about amino acid position 29 in the sequence of FIG.260 (SEQ ID NO:365).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 30 to about 67, inclusive of FIG. 260 (SEQ ID NO:365), or (b) thecomplement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1127 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 through about 80 nucleotides in length,preferably from about 20 through about 60 nucleotides in length, morepreferably from about 20 through about 50 nucleotides in length, andmost preferably from about 20 through about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1127polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1127 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 or 30 through 67 of FIG. 260 (SEQ IDNO:365).

In another aspect, the invention concerns an isolated PRO1127polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 30 to about 67, inclusive of FIG. 260 (SEQ ID NO:365).

In a further aspect, the invention concerns an isolated PRO1127polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 30through 67 of FIG. 260 (SEQ ID NO:365).

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1127 polypeptide having the sequence ofamino acid residues from about 1 or 30 to about 67, inclusive of FIG.260 (SEQ ID NO:365), or (b) the complement of the DNA molecule of (a),and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1127 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1127 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1127 polypeptide, by contactingthe native PRO1127 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1127 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

113. PRO1126

A cDNA clone (DNA60615-1483) has been identified, having homology tonucleic acid encoding olfactomedin that encodes a novel polypeptide,designated in the present application as “PRO1126”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1126 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1126 polypeptide having the sequence of amino acidresidues from about 1 or about 26 to about 402, inclusive of FIG. 262(SEQ ID NO:367), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1126 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about nucleotides 110 orabout 185 and about 1315, inclusive, of FIG. 261 (SEQ ID NO:366).Preferably, hybridization occurs under stringent hybridization and washconditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 209980(DNA60615-1483) or (b) the complement of the nucleic acid molecule of(a). In a preferred embodiment, the nucleic acid comprises a DNAencoding the same mature polypeptide encoded by the human protein cDNAin ATCC Deposit No. 209980 (DNA60615-1483).

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 26 to about 402, inclusive of FIG. 262 (SEQ IDNO:367), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least 10 nucleotides and produced by hybridizing atest DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1126 polypeptide having the sequence of amino acidresidues from 1 or about 26 to about 402, inclusive of FIG. 262 (SEQ IDNO:367), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, preferably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1126 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, or iscomplementary to such encoding nucleic acid molecule. The signal peptidehas been tentatively identified as extending from about amino acidposition 1 to about amino acid position 25 in the sequence of FIG. 262(SEQ ID NO:367).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 26 to about 402, inclusive of FIG. 262 (SEQ ID NO:367), or (b)the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1126 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 261 (SEQ ID NO:366).

In another embodiment, the invention provides isolated PRO1126polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO1126 polypeptide, which in certain embodiments, includes an aminoacid sequence comprising residues 1 or about 26 to about 402 of FIG. 262(SEQ ID NO:367).

In another aspect, the invention concerns an isolated PRO1126polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 26 to about 402, inclusive of FIG. 262 (SEQ ID NO:367).

In a further aspect, the invention concerns an isolated PRO1126polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 26 to about 402, inclusive of FIG. 262 (SEQ ID NO:367).

In yet another aspect, the invention concerns an isolated PRO1126polypeptide, comprising the sequence of amino acid residues 1 or about26 to about 402, inclusive of FIG. 262 (SEQ ID NO:367), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1126antibody. Preferably, the PRO1126 fragment retains a qualitativebiological activity of a native PRO1126 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1126 polypeptide having the sequence ofamino acid residues from about 1 or about 26 to about 402, inclusive ofFIG. 262 (SEQ ID NO:367), or (b) the complement of the DNA molecule of(a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1126 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1126 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1126 polypeptide by contactingthe native PRO1126 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1126 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

114. PRO1125

A cDNA clone (DNA60619-1482) has been identified, having beta-transducinfamily Trp-Asp (WD) conserved regions, that encodes a novel polypeptide,designated in the present application as “PRO1125.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1125 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1125 polypeptide having the sequence of amino acidresidues from about 1 or 26 to about 447, inclusive of FIG. 264 (SEQ IDNO:369), or (b) the complement of the DNA molecule of (a). As usedherein, “or” when referring to nucleic acids or amino acids, refers totwo alternative embodiments, i.e., 1–447 and 26–447.

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1125 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 47 or 122 andabout 1387, inclusive, of FIG. 263 (SEQ ID NO:368). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 209993(DNA60619-1482), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.209993 (DNA60619-1482).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 1 or 26 to about 447, inclusive of FIG. 264(SEQ ID NO:369), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule produced by hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1125 polypeptide havingthe sequence of amino acid residues from about 1 or 26 to about 447,inclusive of FIG. 264 (SEQ ID NO:369), or (b) the complement of the DNAmolecule of (a), and, if the DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), isolating the testDNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1125 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, and itssoluble, i.e. transmembrane domain deleted or inactivated variants, oris complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from amino acidposition 1 through about amino acid position 25 in the sequence of FIG.264 (SEQ ID NO:369).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 26 to about 447, inclusive of FIG. 264 (SEQ ID NO:369), or (b) thecomplement of the DNA of (a).

In another embodiment, the invention provides isolated PRO1125polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1125 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 or 26 to 447 of FIG. 264 (SEQ ID NO:369).

In another aspect, the invention concerns an isolated PRO1125polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 26 to about 447, inclusive of FIG. 264 (SEQ ID NO:369).

In a further aspect, the invention concerns an isolated PRO1125polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 26through 447 of FIG. 264 (SEQ ID NO:369).

In yet another aspect, the invention concerns an isolated PRO1125polypeptide, comprising the sequence of amino acid residues 26 to about447, inclusive of FIG. 264 (SEQ ID NO:369), or a fragment thereofsufficient to provide a binding site for an anti-PRO1125 antibody.Preferably, the PRO1125 fragment retains a qualitative biologicalactivity of a native PRO1125 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1125 polypeptide having the sequence ofamino acid residues from about 26 to about 447, inclusive of FIG. 264(SEQ ID NO:369), or (b) the complement of the DNA molecule of (a), andif the test DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1125 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1125 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1125 polypeptide, by contactingthe native PRO1125 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

115. PRO1186

A cDNA clone (DNA60621-1516) has been identified that encodes a novelpolypeptide having sequence identity with venom protein A and designatedin the present application as “PRO1186.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1186 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1186 polypeptide having the sequence of amino acidresidues from about 20 to about 105, inclusive of FIG. 266 (SEQ IDNO:371), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1186 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 148 and about405, inclusive, of FIG. 265 (SEQ ID NO:370). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203091(DNA60621-1516), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203091 (DNA60621-1516).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 20 to about 105, inclusive of FIG. 266 (SEQ IDNO:371), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least about 50 nucleotides, and preferably at leastabout 100 nucleotides and produced by hybridizing a test DNA moleculeunder stringent conditions with (a) a DNA molecule encoding a PRO1186polypeptide having the sequence of amino acid residues from about 20 toabout 105, inclusive of FIG. 266 (SEQ ID NO:371), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least aboutan 80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 20to about 105, inclusive of FIG. 266 (SEQ ID NO:371), or (b) thecomplement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1186 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 through about 80 nucleotides in length,preferably from about 20 through about 60 nucleotides in length, morepreferably from about 20 through about 50 nucleotides in length, andmost preferably from about 20 through about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1186polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1186 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 20 through 105 of FIG. 266 (SEQ ID NO:371).

In another aspect, the invention concerns an isolated PRO1186polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues20 to about 105, inclusive of FIG. 266 (SEQ ID NO:371).

In a further aspect, the invention concerns an isolated PRO1186polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 20through 105 of FIG. 266 (SEQ ID NO:371).

In yet another aspect, the invention concerns an isolated PRO1186polypeptide, comprising the sequence of amino acid residues 20 to about105, inclusive of FIG. 266 (SEQ ID NO:371), or a fragment thereofsufficient to provide a binding site for an anti-PRO1186 antibody.Preferably, the PRO1186 fragment retains a qualitative biologicalactivity of a native PRO1186 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1186 polypeptide having the sequence ofamino acid residues from about 20 to about 105, inclusive of FIG. 266(SEQ ID NO:371), or (b) the complement of the DNA molecule of (a), andif the test DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1186 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1186 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1186 polypeptide, by contactingthe native PRO1186 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1186 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

116. PRO1198

A cDNA clone (DNA60622-1525) has been identified that encodes a novelsecreted polypeptide designated in the present application as “PRO1198.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1198 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1198 polypeptide having the sequence of amino acidresidues from about 35 to about 229, inclusive of FIG. 268 (SEQ IDNO:373), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1198 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 156 and about740, inclusive, of FIG. 268 (SEQ ID NO:373). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203090(DNA60622-1525), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203090 (DNA60622-1525).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 35 to about 229, inclusive of FIG. 268 (SEQ IDNO:373), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least about 50 nucleotides, and preferably at leastabout 100 nucleotides and produced by hybridizing a test DNA moleculeunder stringent conditions with (a) a DNA molecule encoding a PRO1198polypeptide having the sequence of amino acid residues from about 35 toabout 229, inclusive of FIG. 268 (SEQ ID NO:373), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least aboutan 80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1198 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, or iscomplementary to such encoding nucleic acid molecule. The signal peptidehas been tentatively identified as extending from about amino acidposition 1 through about amino acid position 35 in the sequence of FIG.268 (SEQ ID NO:373).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 35to about 229, inclusive of FIG. 268 (SEQ ID NO:373), or (b) thecomplement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1198 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1198polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1198 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 35 to 229 of FIG. 268 (SEQ ID NO:373).

In another aspect, the invention concerns an isolated PRO1198polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues35 to about 229, inclusive of FIG. 268 (SEQ ID NO:373).

In a further aspect, the invention concerns an isolated PRO1198polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 35 to229 of FIG. 268 (SEQ ID NO:373).

In yet another aspect, the invention concerns an isolated PRO1198polypeptide, comprising the sequence of amino acid residues 35 to about229, inclusive of FIG. 268 (SEQ ID NO:373), or a fragment thereofsufficient to provide a binding site for an anti-PRO1198 antibody.Preferably, the PRO1198 fragment retains a qualitative biologicalactivity of a native PRO1198 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1198 polypeptide having the sequence ofamino acid residues from about 35 to about 229, inclusive of FIG. 268(SEQ ID NO:373), or (b) the complement of the DNA molecule of (a), andif the test DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

117. PRO1158

A cDNA clone (DNA60625-1507) has been identified that encodes a noveltransmembrane polypeptide, designated in the present application as“PRO1158”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1158 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1158 polypeptide having the sequence of amino acidresidues from about 20 to about 123, inclusive of FIG. 270 (SEQ IDNO:375), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1158 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 220 and about531, inclusive, of FIG. 269 (SEQ ID NO:374). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 209975(DNA60625-1507), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.209975 (DNA60625-1507).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 20 to about 123, inclusive of FIG. 270 (SEQ IDNO:375), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least about 50 nucleotides, and preferably at leastabout 100 nucleotides and produced by hybridizing a test DNA moleculeunder stringent conditions with (a) a DNA molecule encoding a PRO1158polypeptide having the sequence of amino acid residues from about 20 toabout 123, inclusive of FIG. 270 (SEQ ID NO:375), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least aboutan 80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1158 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, and itssoluble, i.e. transmembrane domain deleted or inactivated variants, oris complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from about aminoacid position 1 to about amino acid position 19 in the sequence of FIG.270 (SEQ ID NO:375). The transmembrane domain has been tentativelyidentified as extending from about amino acid position 56 to about aminoacid position 80 in the PRO1158 amino acid sequence (FIG. 270, SEQ IDNO:375).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 20to about 123, inclusive of FIG. 270 (SEQ ID NO:375), or (b) thecomplement of the DNA of (a).

In another aspect, the invention concerns hybridization probes thatcomprise fragments of the PRO1158 coding sequence, or complementarysequence thereof. The hybridization probes preferably have at leastabout 20 nucleotides to about 80 nucleotides, and more preferably, atleast about 20 to about 50 nucleotides.

In another embodiment, the invention provides isolated PRO1158polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1158 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 20 to 123 of FIG. 270 (SEQ ID NO:375).

In another aspect, the invention concerns an isolated PRO1158polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues20 to about 123, inclusive of FIG. 270 (SEQ ID NO:375).

In a further aspect, the invention concerns an isolated PRO1158polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 20 to123 of FIG. 270 (SEQ ID NO:375).

In yet another aspect, the invention concerns an isolated PRO1158polypeptide, comprising the sequence of amino acid residues 20 to about123, inclusive of FIG. 270 (SEQ ID NO:375), or a fragment thereofsufficient to provide a binding site for an anti-PRO1158 antibody.Preferably, the PRO1158 fragment retains a qualitative biologicalactivity of a native PRO1158 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1158 polypeptide having the sequence ofamino acid residues from about 20 to about 123, inclusive of FIG. 270(SEQ ID NO:375), or (b) the complement of the DNA molecule of (a), andif the test DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

118. PRO1159

A cDNA clone (DNA60627-1508) has been identified that encodes a novelsecreted polypeptide, designated in the present application as“PRO1159”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1159 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1159 polypeptide having the sequence of amino acidresidues from about 1 or about 16 to about 90, inclusive of FIG. 272(SEQ ID NO:377), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1159 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about nucleotides 92 or about137 and about 361, inclusive, of FIG. 271 (SEQ ID NO:376). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203092(DNA60627-1508) or (b) the complement of the nucleic acid molecule of(a). In a preferred embodiment, the nucleic acid comprises a DNAencoding the same mature polypeptide encoded by the human protein cDNAin ATCC Deposit No. 203092 (DNA60627-1508).

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 16 to about 90, inclusive of FIG. 272 (SEQ IDNO:377), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least 10 nucleotides and produced by hybridizing atest DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1159 polypeptide having the sequence of amino acidresidues from 1 or about 16 to about 90, inclusive of FIG. 272 (SEQ IDNO:377), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, preferably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1159 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, or iscomplementary to such encoding nucleic acid molecule. The signal peptidehas been tentatively identified as extending from about amino acidposition 1 to about amino acid position 15 in the sequence of FIG. 272(SEQ ID NO:377).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 16 to about 90, inclusive of FIG. 272 (SEQ ID NO:377), or (b)the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1159 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 271 (SEQ ID NO:376).

In another embodiment, the invention provides isolated PRO1159polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO1159 polypeptide, which in certain embodiments, includes an aminoacid sequence comprising residues 1 or about 16 to about 90 of FIG. 272(SEQ ID NO:377).

In another aspect, the invention concerns an isolated PRO1159polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 16 to about 90, inclusive of FIG. 272 (SEQ ID NO:377).

In a further aspect, the invention concerns an isolated PRO1159polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 16 to about 90, inclusive of FIG. 272 (SEQ ID NO:377).

In yet another aspect, the invention concerns an isolated PRO1159polypeptide, comprising the sequence of amino acid residues 1 or about16 to about 90, inclusive of FIG. 272 (SEQ ID NO:377), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1159antibody. Preferably, the PRO1159 fragment retains a qualitativebiological activity of a native PRO1159 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1159 polypeptide having the sequence ofamino acid residues from about 1 or about 16 to about 90, inclusive ofFIG. 272 (SEQ ID NO:377), or (b) the complement of the DNA molecule of(a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

119. PRO1124

A cDNA clone (DNA60629-1481) has been identified, having sequenceidentity with a chloride channel protein and lung-endothelial celladhesion molecule-1 (EAM-1) that encodes a novel polypeptide, designatedin the present application as “PRO1124.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1124 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1124 polypeptide having the sequence of amino acidresidues from about 1 or 22 to about 919, inclusive of FIG. 274 (SEQ IDNO:379), or (b) the complement of the DNA molecule of (a). As usedherein, “or”, i.e., 1 or 22 and 25 or 88, is used to describe twoalternative embodiments. For example, the invention includes amino acids1 through 919 and in an alternative embodiment, provides amino acids 22through 919, etc.

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1124 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 25 or 88 andabout 2781, inclusive, of FIG. 273 (SEQ ID NO:378). In another aspect,the invention concerns an isolated nucleic acid molecule hybridizing tothe complement of the nucleic acid of SEQ ID NO:378. Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 209979(DNA60629-1481), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.209979 (DNA60629-1481).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 1 or 22 to about 919, inclusive of FIG. 274(SEQ ID NO:379), or the complement of the DNA of (a).

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1124 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, and itssoluble, i.e. transmembrane domain deleted or inactivated variants, oris complementary to such encoding nucleic acid molecule. The cytoplasmicend can be excluded as well. The signal peptide has been tentativelyidentified as extending from amino acid position 1 to about amino acidposition 21 in the sequence of FIG. 274 (SEQ ID NO:379). Thetransmembrane domains have been tentatively identified as extending fromabout amino acid position 284 to about amino acid position 300 and fromabout amino acid position 617 to about amino acid position 633 in theamino acid sequence (FIG. 274, SEQ ID NO:379).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 22 to about 919, inclusive of FIG. 274 (SEQ ID NO:379), or (b) thecomplement of the DNA of (a).

In another embodiment, the invention provides isolated PRO1124polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1124 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 or 22 through 919 of FIG. 274 (SEQ IDNO:379).

In another aspect, the invention concerns an isolated PRO1124polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 22 to about 919, inclusive of FIG. 274 (SEQ ID NO:379).

In a further aspect, the invention concerns an isolated PRO1124polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 22to 919 of FIG. 274 (SEQ ID NO:379).

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1124 polypeptide having the sequence ofamino acid residues from about 1 or 22 to about 919, inclusive of FIG.274 (SEQ ID NO:379), or (b) the complement of the DNA molecule of (a),and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1124 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1124 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1124 polypeptide, by contactingthe native PRO1124 polypeptide with a candidate molecule and monitoringan activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1124 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

120. PRO1287

A cDNA clone (DNA61755-1554) has been identified, having homology tonucleic acid encoding fringe protein, that encodes a novel polypeptide,designated in the present application as “PRO1287”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1287 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1287 polypeptide having the sequence of amino acidresidues from about 1 or about 28 to about 532, inclusive of FIG. 276(SEQ ID NO:381), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1287 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about nucleotides 655 orabout 736 and about 2250, inclusive, of FIG. 275 (SEQ ID NO:380).Preferably, hybridization occurs under stringent hybridization and washconditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203112(DNA61755-1554) or (b) the complement of the nucleic acid molecule of(a). In a preferred embodiment, the nucleic acid comprises a DNAencoding the same mature polypeptide encoded by the human protein cDNAin ATCC Deposit No. 203112 (DNA61755-1554).

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 28 to about 532, inclusive of FIG. 276 (SEQ IDNO:381), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least 100 nucleotides and produced by hybridizing atest DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1287 polypeptide having the sequence of amino acidresidues from 1 or about 28 to about 532, inclusive of FIG. 276 (SEQ IDNO:381), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, preferably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1287 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, or iscomplementary to such encoding nucleic acid molecule. The signal peptidehas been tentatively identified as extending from about amino acidposition 1 to about amino acid position 27 in the sequence of FIG. 276(SEQ ID NO:381).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 28 to about 532, inclusive of FIG. 276 (SEQ ID NO:381), or (b)the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1287 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 275 (SEQ ID NO:380).

In another embodiment, the invention provides isolated PRO1287polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO1287 polypeptide, which in certain embodiments, includes an aminoacid sequence comprising residues 1 or about 28 to about 532 of FIG. 276(SEQ ID NO:381).

In another aspect, the invention concerns an isolated PRO1287polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 28 to about 532, inclusive of FIG. 276 (SEQ ID NO:381).

In a further aspect, the invention concerns an isolated PRO1287polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 28 to about 532, inclusive of FIG. 276 (SEQ ID NO:381).

In yet another aspect, the invention concerns an isolated PRO1287polypeptide, comprising the sequence of amino acid residues 1 or about28 to about 532, inclusive of FIG. 276 (SEQ ID NO:381), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1287antibody. Preferably, the PRO1287 fragment retains a qualitativebiological activity of a native PRO1287 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1287 polypeptide having the sequence ofamino acid residues from about 1 or about 28 to about 532, inclusive ofFIG. 276 (SEQ ID NO:381), or (b) the complement of the DNA molecule of(a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1287 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1287 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1287 polypeptide by contactingthe native PRO1287 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1287 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

121. PRO1312

A cDNA clone (DNA61873-1574) has been identified that encodes a noveltransmembrane polypeptide designated in the present application as“PRO1312”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1312 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1312 polypeptide having the sequence of amino acidresidues from about 15 to about 212, inclusive of FIG. 278 (SEQ IDNO:387), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1312 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 49 and about642, inclusive, of FIG. 277 (SEQ ID NO:386). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203132(DNA61873-1574), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203132 (DNA61873-1574).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 15 to about 212, inclusive of FIG. 278 (SEQ IDNO:387), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least about 50 nucleotides, and preferably at leastabout 100 nucleotides and produced by hybridizing a test DNA moleculeunder stringent conditions with (a) a DNA molecule encoding a PRO1312polypeptide having the sequence of amino acid residues from about 15 toabout 212, inclusive of FIG. 278 (SEQ ID NO:387), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least aboutan 80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1312 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, and itssoluble, i.e. transmembrane domain deleted or inactivated variants, oris complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from amino acidposition 1 through about amino acid position 14 in the sequence of FIG.278 (SEQ ID NO:387). The transmembrane domain has been tentativelyidentified as extending from about amino acid position 141 to aboutamino acid position 160 in the PRO1312 amino acid sequence (FIG. 278,SEQ ID NO:387).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 15to about 212, inclusive of FIG. 278 (SEQ ID NO:387), or (b) thecomplement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1312 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1312polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1312 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 15 to 212 of FIG. 278 (SEQ ID NO:387).

In another aspect, the invention concerns an isolated PRO1312polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues15 to about 212, inclusive of FIG. 278 (SEQ ID NO:387).

In a further aspect, the invention concerns an isolated PRO1312polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 15 to212 of FIG. 278 (SEQ ID NO:387).

In yet another aspect, the invention concerns an isolated PRO1312polypeptide, comprising the sequence of amino acid residues 15 to about212, inclusive of FIG. 278 (SEQ ID NO:387), or a fragment thereofsufficient to provide a binding site for an anti-PRO1312 antibody.Preferably, the PRO1312 fragment retains a qualitative biologicalactivity of a native PRO1312 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1312 polypeptide having the sequence ofamino acid residues from about 15 to about 212, inclusive of FIG. 278(SEQ ID NO:387), or (b) the complement of the DNA molecule of (a), andif the test DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

122. PRO1192

A cDNA clone (DNA62814-1521) has been identified that encodes a novelpolypeptide having homology to myelin P0 protein and designated in thepresent application as “PRO1192.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1192 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1192 polypeptide having the sequence of amino acidresidues from about 22 to about 215, inclusive of FIG. 280 (SEQ IDNO:389), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1192 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 184 and about764, inclusive, of FIG. 279 (SEQ ID NO:388). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203093(DNA62814-1521), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203093 (DNA62814-1521).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 22 to about 215, inclusive of FIG. 280 (SEQ IDNO:389), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least about 50 nucleotides, and preferably at leastabout 100 nucleotides and produced by hybridizing a test DNA moleculeunder stringent conditions with (a) a DNA molecule encoding a PRO1192polypeptide having the sequence of amino acid residues from about 22 toabout 215, inclusive of FIG. 280 (SEQ ID NO:389), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least aboutan 80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1192 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, and itssoluble, i.e. transmembrane domain deleted or inactivated variants, oris complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from amino acidposition 1 through about amino acid position 21 in the sequence of FIG.280 (SEQ ID NO:389). The transmembrane domain has been tentativelyidentified as extending from about amino acid position 153 through aboutamino acid position 176 in the PRO1192 amino acid sequence (FIG. 280,SEQ ID NO:389).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 22to about 215, inclusive of FIG. 280 (SEQ ID NO:389), or (b) thecomplement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1192 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1192polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1192 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 22 to 215 of FIG. 280 (SEQ ID NO:389).

In another aspect, the invention concerns an isolated PRO1192polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues22 to about 215, inclusive of FIG. 280 (SEQ ID NO:389).

In a further aspect, the invention concerns an isolated PRO1192polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 22 to215 of FIG. 280 (SEQ ID NO:389).

In yet another aspect, the invention concerns an isolated PRO1192polypeptide, comprising the sequence of amino acid residues 22 to about215, inclusive of FIG. 280 (SEQ ID NO:389), or a fragment thereofsufficient to provide a binding site for an anti-PRO1192 antibody.Preferably, the PRO1192 fragment retains a qualitative biologicalactivity of a native PRO1192 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1192 polypeptide having the sequence ofamino acid residues from about 22 to about 215, inclusive of FIG. 280(SEQ ID NO:389), or (b) the complement of the DNA molecule of (a), andif the test DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1192 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1192 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1192 polypeptide, by contactingthe native PRO1192 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1192 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

123. PRO1160

A cDNA clone (DNA62872-1509) has been identified that encodes a novelsecreted polypeptide, designated in the present application as“PRO1160”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1160 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1160 polypeptide having the sequence of amino acidresidues from about 1 or about 20 to about 90, inclusive of FIG. 282(SEQ ID NO:394), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1160 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about nucleotides 40 or about97 and about 309, inclusive, of FIG. 282 (SEQ ID NO:394). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203100(DNA62872-1509) or (b) the complement of the nucleic acid molecule of(a). In a preferred embodiment, the nucleic acid comprises a DNAencoding the same mature polypeptide encoded by the human protein cDNAin ATCC Deposit No. 203100 (DNA62872-1509).

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 20 to about 90, inclusive of FIG. 282 (SEQ IDNO:394), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least 100 nucleotides and produced by hybridizing atest DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1160 polypeptide having tile sequence of amino acidresidues from 1 or about 20 to about 90, inclusive of FIG. 282 (SEQ IDNO:394), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, preferably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1160 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, or iscomplementary to such encoding nucleic acid molecule. The signal peptidehas been tentatively identified as extending from about amino acidposition 1 to about amino acid position 19 in the sequence of FIG. 282(SEQ ID NO:394).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 20 to about 90, inclusive of FIG. 282 (SEQ ID NO:394), or (b)the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1160 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 281 (SEQ ID NO:393).

In another embodiment, the invention provides isolated PRO1160polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO1160 polypeptide, which in certain embodiments, includes an aminoacid sequence comprising residues 1 or about 20 to about 90 of FIG. 282(SEQ ID NO:394).

In another aspect, the invention concerns an isolated PRO1160polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 20 to about 90, inclusive of FIG. 282 (SEQ ID NO:394).

In a further aspect, the invention concerns an isolated PRO1160polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 20 to about 90, inclusive of FIG. 282 (SEQ ID NO:394).

In yet another aspect, the invention concerns an isolated PRO1160polypeptide, comprising the sequence of amino acid residues 1 or about20 to about 90, inclusive of FIG. 282 (SEQ ID NO:394), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1160antibody. Preferably, the PRO1160 fragment retains a qualitativebiological activity of a native PRO1160 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1160 polypeptide having the sequence ofamino acid residues from about 1 or about 20 to about 90, inclusive ofFIG. 282 (SEQ ID NO:394), or (b) the complement of the DNA molecule of(a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

124. PRO1187

A cDNA clone (DNA62876-1517) has been identified that encodes a novelpolypeptide having sequence identity with endo-beta-1,4-xylanase anddesignated in the present application as “PRO1187.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1187 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1187 polypeptide having the sequence of amino acidresidues from about 18 to about 120, inclusive of FIG. 284 (SEQ IDNO:399), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1187 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 172 and about480, inclusive, of FIG. 283 (SEQ ID NO:398). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203095(DNA62876-1517), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203095 (DNA62876-1517).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 18 to about 120, inclusive of FIG. 284 (SEQ IDNO:399), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least about 50 nucleotides, and preferably at leastabout 100 nucleotides and produced by hybridizing a test DNA moleculeunder stringent conditions with (a) a DNA molecule encoding a PRO1187polypeptide having the sequence of amino acid residues from about 18 toabout 120, inclusive of FIG. 284 (SEQ ID NO:399), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least aboutan 80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 18to about 120, inclusive of FIG. 284 (SEQ ID NO:399), or (b) thecomplement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1187 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 through about 80 nucleotides in length,preferably from about 20 through about 60 nucleotides in length, morepreferably from about 20 through about 50 nucleotides in length, andmost preferably from about 20 through about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1187polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1187 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 18 through 120 of FIG. 284 (SEQ ID NO:399).

In another aspect, the invention concerns an isolated PRO1187polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues18 to about 120, inclusive of FIG. 284 (SEQ ID NO:399).

In a further aspect, the invention concerns an isolated PRO1187polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 18through 120 of FIG. 284 (SEQ ID NO:399).

In yet another aspect, the invention concerns an isolated PRO1187polypeptide, comprising the sequence of amino acid residues 18 to about120, inclusive of FIG. 284 (SEQ ID NO:399), or a fragment thereofsufficient to provide a binding site for an anti-PRO1187 antibody.Preferably, the PRO1187 fragment retains a qualitative biologicalactivity of a native PRO1187 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1187 polypeptide having the sequence ofamino acid residues from about 18 to about 120, inclusive of FIG. 284(SEQ ID NO:399), or (b) the complement of the DNA molecule of (a), andif the test DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1187 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1187 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1187 polypeptide, by contactingthe native PRO1187 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1187 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

125. PRO1185

A cDNA clone (DNA62881-1515) has been identified that encodes a novelpolypeptide having sequence identity to a glucose repression regulatoryprotein, tup1, and designated in the present application as “PRO1185.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1185 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1185 polypeptide having the sequence of amino acidresidues from about 22 to about 198, inclusive of FIG. 286 (SEQ IDNO:401), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1185 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 67 and about597, inclusive, of FIG. 285 (SEQ ID NO:400). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203096(DNA62881-1515), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203096 (DNA62881-1515).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 22 to about 198, inclusive of FIG. 286 (SEQ IDNO:401), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least about 50 nucleotides, and preferably at leastabout 100 nucleotides and produced by hybridizing a test DNA moleculeunder stringent conditions with (a) a DNA molecule encoding a PRO1185polypeptide having the sequence of amino acid residues from about 22 toabout 198, inclusive of FIG. 286 (SEQ ID NO:401), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least aboutan 80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 22to about 198, inclusive of FIG. 286 (SEQ ID NO:401), or (b) thecomplement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1185 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 through about 80 nucleotides in length,preferably from about 20 through about 60 nucleotides in length, morepreferably from about 20 through about 50 nucleotides in length, andmost preferably from about 20 through about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1185polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1185 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 22 through 198 of FIG. 286 (SEQ ID NO:401).

In another aspect, the invention concerns an isolated PRO1185polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues22 to about 198, inclusive of FIG. 286 (SEQ ID NO:401).

In a further aspect, the invention concerns an isolated PRO1185polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 22through 198 of FIG. 286 (SEQ ID NO:401).

In yet another aspect, the invention concerns an isolated PRO1185polypeptide, comprising the sequence of amino acid residues 22 to about198, inclusive of FIG. 286 (SEQ ID NO:401), or a fragment thereofsufficient to provide a binding site for an anti-PRO1185 antibody.Preferably, the PRO1185 fragment retains a qualitative biologicalactivity of a native PRO1185 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1185 polypeptide having the sequence ofamino acid residues from about 22 to about 198, inclusive of FIG. 286(SEQ ID NO:401), or (b) the complement of the DNA molecule of (a), andif the test DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1185 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1185 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1185 polypeptide, by contactingthe native PRO1185 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1185 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

126. PRO1345

A cDNA clone (DNA64852-1589) has been identified, having homology tonucleic acid encoding tetranectin protein that encodes a novelpolypeptide, designated in the present application as “PRO1345”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1345 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1345 polypeptide having the sequence of amino acidresidues from about 1 or about 32 to about 206, inclusive of FIG. 288(SEQ ID NO:403), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1345 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about nucleotides 7 or about100 and about 624, inclusive, of FIG. 287 (SEQ ID NO:402). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203127(DNA64852-1589) or (b) the complement of the nucleic acid molecule of(a). In a preferred embodiment, the nucleic acid comprises a DNAencoding the same mature polypeptide encoded by the human protein cDNAin ATCC Deposit No. 203127 (DNA64852-1589).

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 32 to about 206, inclusive of FIG. 288 (SEQ IDNO:403), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least 100 nucleotides and produced by hybridizing atest DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1345 polypeptide having the sequence of amino acidresidues from 1 or about 32 to about 206, inclusive of FIG. 288 (SEQ IDNO:403), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, preferably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1345 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, or iscomplementary to such encoding nucleic acid molecule. The signal peptidehas been tentatively identified as extending from about amino acidposition 1 or amino acid 10 to about amino acid position 31 in thesequence of FIG. 288 (SEQ ID NO:403).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 32 to about 206, inclusive of FIG. 288 (SEQ ID NO:403), or (b)the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1345 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 287 (SEQ ID NO:402).

In another embodiment, the invention provides isolated PRO1345polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO1345 polypeptide, which in certain embodiments, includes an aminoacid sequence comprising residues 1 or about 32 to about 206 of FIG. 288(SEQ ID NO:403).

In another aspect, the invention concerns an isolated PRO1345polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 32 to about 206, inclusive of FIG. 288 (SEQ ID NO:403).

In a further aspect, the invention concerns an isolated PRO1345polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 32 to about 206, inclusive of FIG. 288 (SEQ ID NO:403).

In yet another aspect, the invention concerns an isolated PRO1345polypeptide, comprising the sequence of amino acid residues 1 or about32 to about 206, inclusive of FIG. 288 (SEQ ID NO:403), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1345antibody. Preferably, the PRO1345 fragment retains a qualitativebiological activity of a native PRO1345 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1345 polypeptide having the sequence ofamino acid residues from about 1 or about 32 to about 206, inclusive ofFIG. 288 (SEQ ID NO:403), or (b) the complement of the DNA molecule of(a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1345 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1345 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of oa native PRO1345 polypeptide by contactingthe native PRO1345 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1345 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

127. PRO1245

A cDNA clone (DNA64884-1527) has been identified that encodes a novelsecreted polypeptide designated in the present application as “PRO1245.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1245 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1245 polypeptide having the sequence of amino acidresidues from about 19 to about 104, inclusive of FIG. 290 (SEQ IDNO:408), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1245 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 133 and about390, inclusive, of FIG. 289 (SEQ ID NO:407). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203155(DNA64884-1245), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203155 (DNA64884-1245).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 19 to about 104, inclusive of FIG. 290 (SEQ IDNO:408), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least about 50 nucleotides, and preferably at leastabout 100 nucleotides and produced by hybridizing a test DNA moleculeunder stringent conditions with (a) a DNA molecule encoding a PRO1245polypeptide having the sequence of amino acid residues from about 19 toabout 104, inclusive of FIG. 290 (SEQ ID NO:408), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least aboutan 80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1245 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, or iscomplementary to such encoding nucleic acid molecule. The signal peptidehas been tentatively identified as extending from amino acid position 1through about amino acid position 18 in the sequence of FIG. 290 (SEQ IDNO:408).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 19to about 104, inclusive of FIG. 290 (SEQ ID NO:408), or (b) thecomplement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1245 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1245polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1245 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 19 to 104 of FIG. 290 (SEQ ID NO:408).

In another aspect, the invention concerns an isolated PRO1245polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues19 to about 104, inclusive of FIG. 290 (SEQ ID NO:408).

In a further aspect, the invention concerns an isolated PRO1245polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 19 to104 of FIG. 290 (SEQ ID NO:408).

In yet another aspect, the invention concerns an isolated PRO1245polypeptide, comprising the sequence of amino acid residues 19 to about104, inclusive of FIG. 290 (SEQ ID NO:408), or a fragment thereofsufficient to provide a binding site for an anti-PRO1245 antibody.Preferably, the PRO1245 fragment retains a qualitative biologicalactivity of a native PRO1245 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1245 polypeptide having the sequence ofamino acid residues from about 19 to about 104, inclusive of FIG. 290(SEQ ID NO:408), or (b) the complement of the DNA molecule of (a), andif the test DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

128. PRO1358

A cDNA clone (DNA64890-1612) has been identified that encodes a novelpolypeptide having sequence identity with RASP-1 and designated in thepresent application as “PRO1358.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1358 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1358 polypeptide having the sequence of amino acidresidues from about 19 to about 444, inclusive of FIG. 292 (SEQ IDNO:410), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1358 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 140 and about1417, inclusive, of FIG. 292 (SEQ ID NO:410). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203131(DNA64890-1612), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203131 (DNA64890-1612).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 19 to about 444, inclusive of FIG. 292 (SEQ IDNO:410), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least about 50 nucleotides, and preferably at leastabout 100 nucleotides and produced by hybridizing a test DNA moleculeunder stringent conditions with (a) a DNA molecule encoding a PRO1358polypeptide having the sequence of amino acid residues from about 19 toabout 444, inclusive of FIG. 292 (SEQ ID NO:410), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least aboutan 80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 19to about 444, inclusive of FIG. 292 (SEQ ID NO:410), or (b) thecomplement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1358 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 80 nucleotides to about 120 nucleotides inlength.

In another embodiment, the invention provides isolated PRO1358polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1358 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 19 through 444 of FIG. 292 (SEQ ID NO:410).

In another aspect, the invention concerns an isolated PRO1358polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues19 to about 444, inclusive of FIG. 292 (SEQ ID NO:410).

In a further aspect, the invention concerns an isolated PRO1358polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 19through 444 of FIG. 292 (SEQ ID NO:410).

In yet another aspect, the invention concerns an isolated PRO1358polypeptide, comprising the sequence of amino acid residues 19 to about444, inclusive of FIG. 292 (SEQ ID NO:410), or a fragment thereofsufficient to provide a binding site for an anti-PRO1358 antibodyspecific therefore. Preferably, the PRO1358 fragment retains aqualitative biological activity of a native PRO1358 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1358 polypeptide having the sequence ofamino acid residues from about 19 to about 444, inclusive of FIG. 292(SEQ ID NO:410), or (b) the complement of the DNA molecule of (a), andif the test DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1358 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1358 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1358 polypeptide, by contactingthe native PRO1358 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1358 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

129. PRO1195

A cDNA clone (DNA65412-1523) has been identified that encodes a novelpolypeptide having sequence identity with a mouse proline rich acidicprotein and designated in the present application as “PRO1195.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1195 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1195 polypeptide having the sequence of amino acidresidues from about 23 to about 151, inclusive of FIG. 294 (SEQ IDNO:412), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1195 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 124 and about510, inclusive, of FIG. 293 (SEQ ID NO:411). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203094(DNA65412-1523), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203094 (DNA65412-1523).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 23 to about 151, inclusive of FIG. 294 (SEQ IDNO:412), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least about 50 nucleotides, and preferably at leastabout 100 nucleotides and produced by hybridizing a test DNA moleculeunder stringent conditions with (a) a DNA molecule encoding a PRO1195polypeptide having the sequence of amino acid residues from about 23 toabout 151, inclusive of FIG. 294 (SEQ ID NO:412), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least aboutan 80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 23to about 151, inclusive of FIG. 294 (SEQ ID NO:412), or (b) thecomplement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1195 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 through about 80 nucleotides in length,preferably from about 20 through about 60 nucleotides in length, morepreferably from about 20 through about 50 nucleotides in length, andmost preferably from about 20 through about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1195polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1195 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 23 through 151 of FIG. 294 (SEQ ID NO:412).

In another aspect, the invention concerns an isolated PRO1195polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues23 to about 151, inclusive of FIG. 294 (SEQ ID NO:412).

In a further aspect, the invention concerns an isolated PRO1195polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 23through 151 of FIG. 294 (SEQ ID NO:412).

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1195 polypeptide having the sequence ofamino acid residues from about 23 to about 151, inclusive of FIG. 294(SEQ ID NO:412), or (b) the complement of the DNA molecule of (a), andif the test DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1195 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1195 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1195 polypeptide, by contactingthe native PRO1195 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1195 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

130. PRO1270

A cDNA clone (DNA66308-1537) has been identified, having homology tonucleic acid encoding a lectin protein, that encodes a novelpolypeptide, designated in the present application as “PRO1270”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1270 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1270 polypeptide having the sequence of amino acidresidues from about 1 or about 17 to about 313, inclusive of FIG. 296(SEQ ID NO:414), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1270 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about nucleotides 103 orabout 151 and about 1041, inclusive, of FIG. 295 (SEQ ID NO:413).Preferably, hybridization occurs under stringent hybridization and washconditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203159(DNA66308-1537) or (b) the complement of the nucleic acid molecule of(a). In a preferred embodiment, the nucleic acid comprises a DNAencoding the same mature polypeptide encoded by the human protein cDNAin ATCC Deposit No. 203159 (DNA66308-1537).

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 17 to about 313, inclusive of FIG. 296 (SEQ IDNO:414), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least 285 nucleotides and produced by hybridizing atest DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1270 polypeptide having the sequence of amino acidresidues from 1 or about 17 to about 313, inclusive of FIG. 296 (SEQ IDNO:414), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, preferably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1270 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, or iscomplementary to such encoding nucleic acid molecule. The signal peptidehas been tentatively identified as extending from about amino acidposition 1 to about amino acid position 16 in the sequence of FIG. 296(SEQ ID NO:414).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 17 to about 313, inclusive of FIG. 296 (SEQ ID NO:414), or (b)the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1270 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 295 (SEQ ID NO:413).

In another embodiment, the invention provides isolated PRO1270polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO1270 polypeptide, which in certain embodiments, includes an aminoacid sequence comprising residues 1 or about 17 to about 313 of FIG. 296(SEQ ID NO:414).

In another aspect, the invention concerns an isolated PRO1270polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 17 to about 313, inclusive of FIG. 296 (SEQ ID NO:414).

In a further aspect, the invention concerns an isolated PRO1270polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 17 to about 313, inclusive of FIG. 296 (SEQ ID NO:414).

In yet another aspect, the invention concerns an isolated PRO1270polypeptide, comprising the sequence of amino acid residues 1 or about17 to about 313, inclusive of FIG. 296 (SEQ ID NO:414), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1270antibody. Preferably, the PRO1270 fragment retains a qualitativebiological activity of a native PRO1270 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1270 polypeptide having the sequence ofamino acid residues from about 1 or about 17 to about 313, inclusive ofFIG. 296 (SEQ ID NO:414), or (b) the complement of the DNA molecule of(a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1270 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1270 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1270 polypeptide by contactingthe native PRO1270 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1270 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

131. PRO1271

A cDNA clone (DNA66309-1538) has been identified that encodes a novelpolypeptide having serine and threonine rich regions designated in thepresent application as “PRO1271” polypeptides.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1271 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1271 polypeptide having the sequence of amino acidresidues from about 32 to about 208, inclusive of FIG. 298 (SEQ IDNO:416), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1271 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 187 and about717, inclusive, of FIG. 297 (SEQ ID NO:415). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203235(DNA66309-1538), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203235 (DNA66309-1538).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 32 to about 208, inclusive of FIG. 298 (SEQ IDNO:416), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least about 50 nucleotides, and preferably at leastabout 100 nucleotides and produced by hybridizing a test DNA moleculeunder stringent conditions with (a) a DNA molecule encoding a PRO1271polypeptide having the sequence of amino acid residues from about 32 toabout 208, inclusive of FIG. 298 (SEQ ID NO:416), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least aboutan 80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1271 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, and itssoluble, i.e. transmembrane domain deleted or inactivated variants, oris complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from amino acidposition 1 through about amino acid position 31 in the sequence of FIG.298 (SEQ ID NO:416). The transmembrane domain has been tentativelyidentified as extending from about amino acid position 166 through aboutamino acid position 187 in the PRO1271 amino acid sequence (FIG. 298,SEQ ID NO:416).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 32to about 208, inclusive of FIG. 298 (SEQ ID NO:416), or (b) thecomplement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1271 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1271polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1271 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 32 through 208 of FIG. 298 (SEQ ID NO:416).

In another aspect, the invention concerns an isolated PRO1271polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues32 to about 208, inclusive of FIG. 298 (SEQ ID NO:416).

In a further aspect, the invention concerns an isolated PRO1271polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 32through 208 of FIG. 298 (SEQ ID NO:416).

In yet another aspect, the invention concerns an isolated PRO1271polypeptide, comprising the sequence of amino acid residues 32 to about208, inclusive of FIG. 298 (SEQ ID NO:416), or a fragment thereofsufficient to provide a binding site for an anti-PRO1271 antibody.Preferably, the PRO1271 fragment retains a qualitative biologicalactivity of a native PRO1271 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1271 polypeptide having the sequence ofamino acid residues from about 32 to about 208, inclusive of FIG. 298(SEQ ID NO:416), or (b) the complement of the DNA molecule of (a), andif the test DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1271 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1271 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1271 polypeptide, by contactingthe native PRO1271 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1271 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

132. PRO1375

A cDNA clone (DNA67004-1614) has been identified that encodes a novelpolypeptide having sequence identity with PUT2 and designated in thepresent application as “PRO1375.”

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1375 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1375 polypeptide having the sequence of amino acidresidues from about 1 to about 198, inclusive of FIG. 300 (SEQ IDNO:418), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1375 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 104 and about697, inclusive, of FIG. 299 (SEQ ID NO:417). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203115(DNA67004-1614), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203115 (DNA67004-1614).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 1 to about 198, inclusive of FIG. 300 (SEQ IDNO:418), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least about 50 nucleotides, and preferably at leastabout 100 nucleotides and produced by hybridizing a test DNA moleculeunder stringent conditions with (a) a DNA molecule encoding a PRO1375polypeptide having the sequence of amino acid residues from about 1 toabout 198, inclusive of FIG. 300 (SEQ ID NO:418), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least aboutan 80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1375 polypeptide in its solubleform, i.e. transmembrane domains deleted or inactivated variants, or iscomplementary to such encoding nucleic acid molecule. The transmembranedomains have been tentatively identified as at about amino acidpositions 11–28 (type II) and 103–125 of SEQ ID NO:418.

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1to about 198, inclusive of FIG. 300 (SEQ ID NO:418), or (b) thecomplement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1375 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1375polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1375 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 through 198 of FIG. 300 (SEQ ID NO:418).

In another aspect, the invention concerns an isolated PRO1375polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 to about 198, inclusive of FIG. 300 (SEQ ID NO:418).

In a further aspect, the invention concerns an isolated PRO1375polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1through 198 of FIG. 300 (SEQ ID NO:418).

In yet another aspect, the invention concerns an isolated PRO1375polypeptide, comprising the sequence of amino acid residues 1 to about198, inclusive of FIG. 300 (SEQ ID NO:418), or a fragment thereofsufficient to provide a binding site for an anti-PRO1375 antibody.Preferably, the PRO1375 fragment retains a qualitative biologicalactivity of a native PRO1375 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1375 polypeptide having the sequence ofamino acid residues from about 1 to about 198, inclusive of FIG. 300(SEQ ID NO:418), or (b) the complement of the DNA molecule of (a), andif the test DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1375 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1375 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1375 polypeptide, by contactingthe native PRO1375 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1375 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

133. PRO1385

A cDNA clone (DNA68869-1610) has been identified that encodes a novelsecreted polypeptide, designated in the present application as“PRO1385”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1385 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1385 polypeptide having the sequence of amino acidresidues from about 1 or about 29 to about 128, inclusive of FIG. 302(SEQ ID NO:420), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1385 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about nucleotides 26 or about110 and about 409, inclusive, of FIG. 301 (SEQ ID NO:419). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203164(DNA68869-1610) or (b) the complement of the nucleic acid molecule of(a). In a preferred embodiment, the nucleic acid comprises a DNAencoding the same mature polypeptide encoded by the human protein cDNAin ATCC Deposit No. 203164 (DNA68869-1610).

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 29 to about 128, inclusive of FIG. 302 (SEQ IDNO:420), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least 245 nucleotides and produced by hybridizing atest DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1385 polypeptide having the sequence of amino acidresidues from 1 or about 29 to about 128, inclusive of FIG. 302 (SEQ IDNO:420), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, preferably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1385 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, or iscomplementary to such encoding nucleic acid molecule. The signal peptidehas been tentatively identified as extending from about amino acidposition 1 to about amino acid position 28 in the sequence of FIG. 302(SEQ ID NO:420).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 29 to about 128, inclusive of FIG. 302 (SEQ ID NO:420), or (b)the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1385 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 301 (SEQ ID NO:419).

In another embodiment, the invention provides isolated PRO1385polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO1385 polypeptide, which in certain embodiments, includes an aminoacid sequence comprising residues 1 or about 29 to about 128 of FIG. 302(SEQ ID NO:420).

In another aspect, the invention concerns an isolated PRO1385polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 29 to about 128, inclusive of FIG. 302 (SEQ ID NO:420).

In a further aspect, the invention concerns an isolated PRO1385polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 29 to about 128, inclusive of FIG. 302 (SEQ ID NO:420).

In yet another aspect, the invention concerns an isolated PRO1385polypeptide, comprising the sequence of amino acid residues 1 or about29 to about 128, inclusive of FIG. 302 (SEQ ID NO:420), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1385antibody. Preferably, the PRO1385 fragment retains a qualitativebiological activity of a native PRO1385 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1385 polypeptide having the sequence ofamino acid residues from about 1 or about 29 to about 128, inclusive ofFIG. 302 (SEQ ID NO:420), or (b) the complement of the DNA molecule of(a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

134. PRO1387

A cDNA clone (DNA68872-1620) has been identified, having homology tonucleic acid encoding myelin, that encodes a novel polypeptide,designated in the present application as “PRO1387”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1387 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1387 polypeptide having the sequence of amino acidresidues from about 1 or about 20 to about 394, inclusive of FIG. 304(SEQ ID NO:422), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1387 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about nucleotides 85 or about142 and about 1266, inclusive, of FIG. 303 (SEQ ID NO:421). Preferably,hybridization occurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203160(DNA68872-1620) or (b) the complement of the nucleic acid molecule of(a). In a preferred embodiment, the nucleic acid comprises a DNAencoding the same mature polypeptide encoded by the human protein cDNAin ATCC Deposit No. 203160 (DNA68872-1620).

In still a further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 20 to about 394, inclusive of FIG. 304 (SEQ IDNO:422), or (b) the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least 395 nucleotides and produced by hybridizing atest DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1387 polypeptide having the sequence of amino acidresidues from 1 or about 20 to about 394, inclusive of FIG. 304 (SEQ IDNO:422), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, preferably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1387 polypeptide, with or withoutthe N-terminal signal sequence and/or the initiating methionine, and itssoluble, i.e., transmembrane domain deleted or inactivated variants, oris complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from about aminoacid position 1 to about amino acid position 19 in the sequence of FIG.304 (SEQ ID NO:422). The transmembrane domain has been tentativelyidentified as extending from about amino acid position 275 to aboutamino acid position 296 in the PRO1387 amino acid sequence (FIG. 304,SEQ ID NO:422).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 20 to about 394, inclusive of FIG. 304 (SEQ ID NO:422), or (b)the complement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1387 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 303 (SEQ ID NO:421).

In another embodiment, the invention provides isolated PRO1387polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

In a specific aspect, the invention provides isolated native sequencePRO1387 polypeptide, which in certain embodiments, includes an aminoacid sequence comprising residues 1 or about 20 to about 394 of FIG. 304(SEQ ID NO:422).

In another aspect, the invention concerns an isolated PRO1387polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 20 to about 394, inclusive of FIG. 304 (SEQ ID NO:422).

In a further aspect, the invention concerns an isolated PRO1387polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 20 to about 394, inclusive of FIG. 304 (SEQ ID NO:422).

In yet another aspect, the invention concerns an isolated PRO1387polypeptide, comprising the sequence of amino acid residues 1 or about20 to about 394, inclusive of FIG. 304 (SEQ ID NO:422), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1387antibody. Preferably, the PRO1387 fragment retains a qualitativebiological activity of a native PRO1387 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1387 polypeptide having the sequence ofamino acid residues from about 1 or about 20 to about 394, inclusive ofFIG. 304 (SEQ ID NO:422), or (b) the complement of the DNA molecule of(a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1387 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1387 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1387 polypeptide by contactingthe native PRO1387 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1387 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

135. PRO1384

A cDNA clone, referred to herein as “DNA71159”, has been identified thatencodes a novel polypeptide having homology to NKG2-D protein designatedin the present application as “PRO1384”.

In one embodiment, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1384 polypeptide.

In one aspect, the isolated nucleic acid comprises DNA having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO1384 polypeptide having the sequence of amino acidresidues from about 1 to about 229, inclusive of FIG. 306 (SEQ IDNO:424), or (b) the complement of the DNA molecule of (a).

In another aspect, the invention concerns an isolated nucleic acidmolecule encoding a PRO1384 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about residues 182 and about868, inclusive, of FIG. 305 (SEQ ID NO:423). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising DNA having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity to (a) a DNA molecule encoding the same maturepolypeptide encoded by the human protein cDNA in ATCC Deposit No. 203135(DNA71159-1617), or (b) the complement of the DNA molecule of (a). In apreferred embodiment, the nucleic acid comprises a DNA encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.203135 (DNA71159-1617).

In a still further aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues from about 1 to about 229, inclusive of FIG. 306 (SEQ IDNO:424), or the complement of the DNA of (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule having at least about 50 nucleotides, and preferably at leastabout 100 nucleotides and produced by hybridizing a test DNA moleculeunder stringent conditions with (a) a DNA molecule encoding a PRO1384polypeptide having the sequence of amino acid residues from about 1 toabout 229, inclusive of FIG. 306 (SEQ ID NO:424), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least aboutan 80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

In a specific aspect, the invention provides an isolated nucleic acidmolecule comprising DNA encoding a PRO1384 polypeptide with itstransmembrane domain deleted or inactivated, or is complementary to suchencoding nucleic acid molecule. The transmembrane domain has beententatively identified as extending from about amino acid position 32through about amino acid position 57 in the PRO1384 amino acid sequence(FIG. 306, SEQ ID NO:424).

In another aspect, the invention concerns an isolated nucleic acidmolecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1to about 229, inclusive of FIG. 306 (SEQ ID NO:424), or (b) thecomplement of the DNA of (a).

Another embodiment is directed to fragments of a PRO1384 polypeptidecoding sequence that may find use as hybridization probes. Such nucleicacid fragments are from about 20 to about 80 nucleotides in length,preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

In another embodiment, the invention provides isolated PRO1384polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

In a specific aspect, the invention provides isolated native sequencePRO1384 polypeptide, which in one embodiment, includes an amino acidsequence comprising residues 1 to 229 of FIG. 306 (SEQ ID NO:424).

In another aspect, the invention concerns an isolatedPRO1384polypeptide, comprising an amino acid sequence having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 to about 229, inclusive of FIG. 306 (SEQ ID NO:424).

In a further aspect, the invention concerns an isolated PRO1384polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 to229 of FIG. 306 (SEQ ID NO:424).

In yet another aspect, the invention concerns an isolated PRO1384polypeptide, comprising the sequence of amino acid residues 1 to about229, inclusive of FIG. 306 (SEQ ID NO:424), or a fragment thereofsufficient to provide a binding site for an anti-PRO1384 antibody.Preferably, the PRO1384 fragment retains a qualitative biologicalactivity of a native PRO1384 polypeptide.

In a still further aspect, the invention provides a polypeptide producedby (i) hybridizing a test DNA molecule under stringent conditions with(a) a DNA molecule encoding a PRO1384 polypeptide having the sequence ofamino acid residues from about 1 to about 229, inclusive of FIG. 306(SEQ ID NO:424), or (b) the complement of the DNA molecule of (a), andif the test DNA molecule has at least about an 80% sequence identity,preferably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), (ii) culturing a host cellcomprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1384 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1384 antibody.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists of a native PRO1384 polypeptide, by contactingthe native PRO1384 polypeptide with a candidate molecule and monitoringa biological activity mediated by said polypeptide.

In a still further embodiment, the invention concerns a compositioncomprising a PRO1384 polypeptide, or an agonist or antagonist ashereinabove defined, in combination with a pharmaceutically acceptablecarrier.

136. Additional Embodiments

In other embodiments of the present invention, the invention providesvectors comprising DNA encoding any of the herein describedpolypeptides. Host cell comprising any such vector are also provided. Byway of example, the host cells may be CHO cells, E. coli, or yeast. Aprocess for producing any of the herein described polypeptides isfurther provided and comprises culturing host cells under conditionssuitable for expression of the desired polypeptide and recovering thedesired polypeptide from the cell culture.

In other embodiments, the invention provides chimeric moleculescomprising any of the herein described polypeptides fused to aheterologous polypeptide or amino acid sequence. Example of suchchimeric molecules comprise any of the herein described polypeptidesfused to an epitope tag sequence or a Fc region of an immunoglobulin.

In another embodiment, the invention provides an antibody whichspecifically binds to any of the above or below described polypeptides.Optionally, the antibody is a monoclonal antibody, humanized antibody,antibody fragment or single-chain antibody.

In yet other embodiments, the invention provides oligonucleotide probesuseful for isolating genomic and cDNA nucleotide sequences or asantisense probes, wherein those probes may be derived from any of theabove or below described nucleotide sequences.

In other embodiments, the invention provides an isolated nucleic acidmolecule comprising a nucleotide sequence that encodes a PROpolypeptide.

In one aspect, the isolated nucleic acid molecule comprises a nucleotidesequence having at least about 80% sequence identity, preferably atleast about 81% sequence identity, more preferably at least about 82%sequence identity, yet more preferably at least about 83% sequenceidentity, yet more preferably at least about 84% sequence identity, yetmore preferably at least about 85% sequence identity, yet morepreferably at least about 86% sequence identity, yet more preferably atleast about 87% sequence identity, yet more preferably at least about88% sequence identity, yet more preferably at least about 89% sequenceidentity, yet more preferably at least about 90% sequence identity, yetmore preferably at least about 91% sequence identity, yet morepreferably at least about 92% sequence identity, yet more preferably atleast about 93% sequence identity, yet more preferably at least about94% sequence identity, yet more preferably at least about 95% sequenceidentity, yet more preferably at least about 96% sequence identity, yetmore preferably at least about 97% sequence identity, yet morepreferably at least about 98% sequence identity and yet more preferablyat least about 99% sequence identity to (a) a DNA molecule encoding aPRO polypeptide having a full-length amino acid sequence as disclosedherein, an amino acid sequence lacking the signal peptide as disclosedherein, an extracellular domain of a transmembrane protein, with orwithout the signal peptide, as disclosed herein or any otherspecifically defined fragment of the full-length amino acid sequence asdisclosed herein, or (b) the complement of the DNA molecule of (a).

In other aspects, the isolated nucleic acid molecule comprises anucleotide sequence having at least about 80% sequence identity,preferably at least about 81% sequence identity, more preferably atleast about 82% sequence identity, yet more preferably at least about83% sequence identity, yet more preferably at least about 84% sequenceidentity, yet more preferably at least about 85% sequence identity, yetmore preferably at least about 86% sequence identity, yet morepreferably at least about 87% sequence identity, yet more preferably atleast about 88% sequence identity, yet more preferably at least about89% sequence identity, yet more preferably at least about 90% sequenceidentity, yet more preferably at least about 91% sequence identity, yetmore preferably at least about 92% sequence identity, yet morepreferably at least about 93% sequence identity, yet more preferably atleast about 94% sequence identity, yet more preferably at least about95% sequence identity, yet more preferably at least about 96% sequenceidentity, yet more preferably at least about 97% sequence identity, yetmore preferably at least about 98% sequence identity and yet morepreferably at least about 99% sequence identity to (a) a DNA moleculecomprising the coding sequence of a full-length PRO polypeptide cDNA asdisclosed herein, the coding sequence of a PRO polypeptide lacking thesignal peptide as disclosed herein, the coding sequence of anextracellular domain of a transmembrane PRO polypeptide, with or withoutthe signal peptide, as disclosed herein or the coding sequence of anyother specifically defined fragment of the full-length amino acidsequence as disclosed herein, or (b) the complement of the DNA moleculeof (a).

In a further aspect, the invention concerns an isolated nucleic acidmolecule comprising a nucleotide sequence having at least about 80%sequence identity, preferably at least about 81% sequence identity, morepreferably at least about 82% sequence identity, yet more preferably atleast about 83% sequence identity, yet more preferably at least about84% sequence identity, yet more preferably at least about 85% sequenceidentity, yet more preferably at least about 86% sequence identity, yetmore preferably at least about 87% sequence identity, yet morepreferably at least about 88% sequence identity, yet more preferably atleast about 89% sequence identity, yet more preferably at least about90% sequence identity, yet more preferably at least about 91% sequenceidentity, yet more preferably at least about 92% sequence identity, yetmore preferably at least about 93% sequence identity, yet morepreferably at least about 94% sequence identity, yet more preferably atleast about 95% sequence identity, yet more preferably at least about96% sequence identity, yet more preferably at least about 97% sequenceidentity, yet more preferably at least about 98% sequence identity andyet more preferably at least about 99% sequence identity to (a) a DNAmolecule that encodes the same mature polypeptide encoded by any of thehuman protein cDNAs deposited with the ATCC as disclosed herein, or (b)the complement of the DNA molecule of (a).

Another aspect the invention provides an isolated nucleic acid moleculecomprising a nucleotide sequence encoding a PRO polypeptide which iseither transmembrane domain-deleted or transmembrane domain-inactivated,or is complementary to such encoding nucleotide sequence, wherein thetransmembrane domain(s) of such polypeptide are disclosed herein.Therefore, soluble extracellular domains of the herein described PROpolypeptides are contemplated.

Another embodiment is directed to fragments of a PRO polypeptide codingsequence, or the complement thereof, that may find use as, for example,hybridization probes, for encoding fragments of a PRO polypeptide thatmay optionally encode a polypeptide comprising a binding site for ananti-PRO antibody or as antisense oligonucleotide probes. Such nucleicacid fragments are usually at least about 20 nucleotides in length,preferably at least about 30 nucleotides in length, more preferably atleast about 40 nucleotides in length, yet more preferably at least about50 nucleotides in length, yet more preferably at least about 60nucleotides in length, yet more preferably at least about 70 nucleotidesin length, yet more preferably at least about 80 nucleotides in length,yet more preferably at least about 90 nucleotides in length, yet morepreferably at least about 100 nucleotides in length, yet more preferablyat least about 110 nucleotides in length, yet more preferably at leastabout 120 nucleotides in length, yet more preferably at least about 130nucleotides in length, yet more preferably at least about 140nucleotides in length, yet more preferably at least about 150nucleotides in length, yet more preferably at least about 160nucleotides in length, yet more preferably at least about 170nucleotides in length, yet more preferably at least about 180nucleotides in length, yet more preferably at least about 190nucleotides in length, yet more preferably at least about 200nucleotides in length, yet more preferably at least about 250nucleotides in length, yet more preferably at least about 300nucleotides in length, yet more preferably at least about 350nucleotides in length, yet more preferably at least about 400nucleotides in length, yet more preferably at least about 450nucleotides in length, yet more preferably at least about 500nucleotides in length, yet more preferably at least about 600nucleotides in length, yet more preferably at least about 700nucleotides in length, yet more preferably at least about 800nucleotides in length, yet more preferably at least about 900nucleotides in length and yet more preferably at least about 1000nucleotides in length, wherein in this context the term “about” meansthe referenced nucleotide sequence length plus or minus 10% of thatreferenced length. It is noted that novel fragments of a PROpolypeptide-encoding nucleotide sequence may be determined in a routinemanner by aligning the PRO polypeptide-encoding nucleotide sequence withother known nucleotide sequences using any of a number of well knownsequence alignment programs and determining which PROpolypeptide-encoding nucleotide sequence fragment(s) are novel. All ofsuch PRO polypeptide-encoding nucleotide sequences are contemplatedherein. Also contemplated are the PRO polypeptide fragments encoded bythese nucleotide molecule fragments, preferably those PRO polypeptidefragments that comprise a binding site for an anti-PRO antibody.

In another embodiment, the invention provides isolated PRO polypeptideencoded by any of the isolated nucleic acid sequences hereinaboveidentified.

In a certain aspect, the invention concerns an isolated PRO polypeptide,comprising an amino acid sequence having at least about 80% sequenceidentity, preferably at least about 81% sequence identity, morepreferably at least about 82% sequence identity, yet more preferably atleast about 83% sequence identity, yet more preferably at least about84% sequence identity, yet more preferably at least about 85% sequenceidentity, yet more preferably at least about 86% sequence identity, yetmore preferably at least about 87% sequence identity, yet morepreferably at least about 88% sequence identity, yet more preferably atleast about 89% sequence identity, yet more preferably at least about90% sequence identity, yet more preferably at least about 91% sequenceidentity, yet more preferably at least about 92% sequence identity, yetmore preferably at least about 93% sequence identity, yet morepreferably at least about 94% sequence identity, yet more preferably atleast about 95% sequence identity, yet more preferably at least about96% sequence identity, yet more preferably at least about 97% sequenceidentity, yet more preferably at least about 98% sequence identity andyet more preferably at least about 99% sequence identity to a PROpolypeptide having a full-length amino acid sequence as disclosedherein, an amino acid sequence lacking the signal peptide as disclosedherein, an extracellular domain of a transmembrane protein, with orwithout the signal peptide, as disclosed herein or any otherspecifically defined fragment of the full-length amino acid sequence asdisclosed herein.

In a further aspect, the invention concerns an isolated PRO polypeptidecomprising an amino acid sequence having at least about 80% sequenceidentity, preferably at least about 81% sequence identity, morepreferably at least about 82% sequence identity, yet more preferably atleast about 83% sequence identity, yet more preferably at least about84% sequence identity, yet more preferably at least about 85% sequenceidentity, yet more preferably at least about 86% sequence identity, yetmore preferably at least about 87% sequence identity, yet morepreferably at least about 88% sequence identity, yet more preferably atleast about 89% sequence identity, yet more preferably at least about90% sequence identity, yet more preferably at least about 91% sequenceidentity, yet more preferably at least about 92% sequence identity, yetmore preferably at least about 93% sequence identity, yet morepreferably at least about 94% sequence identity, yet more preferably atleast about 95% sequence identity, yet more preferably at least about96% sequence identity, yet more preferably at least about 97% sequenceidentity, yet more preferably at least about 98% sequence identity andyet more preferably at least about 99% sequence identity to an aminoacid sequence encoded by any of the human protein cDNAs deposited withthe ATCC as disclosed herein.

In a further aspect, the invention concerns an isolated PRO polypeptidecomprising an amino acid sequence scoring at least about 80% positives,preferably at least about 81% positives, more preferably at least about82% positives, yet more preferably at least about 83% positives, yetmore preferably at least about 84% positives, yet more preferably atleast about 85% positives, yet more preferably at least about 86%positives, yet more preferably at least about 87% positives, yet morepreferably at least about 88% positives, yet more preferably at leastabout 89% positives, yet more preferably at least about 90% positives,yet more preferably at least about 91% positives, yet more preferably atleast about 92% positives, yet more preferably at least about 93%positives, yet more preferably at least about 94% positives, yet morepreferably at least about 95% positives, yet more preferably at leastabout 96% positives, yet more preferably at least about 97% positives,yet more preferably at least about 98% positives and yet more preferablyat least about 99% positives when compared with the amino acid sequenceof a PRO polypeptide having a full-length amino acid sequence asdisclosed herein, an amino acid sequence lacking the signal peptide asdisclosed herein, an extracellular domain of a transmembrane protein,with or without the signal peptide, as disclosed herein or any otherspecifically defined fragment of the full-length amino acid sequence asdisclosed herein.

In a specific aspect, the invention provides an isolated PRO polypeptidewithout the N-terminal signal sequence and/or the initiating methionineand is encoded by a nucleotide sequence that encodes such an amino acidsequence as hereinbefore described. Processes for producing the same arealso herein described, wherein those processes comprise culturing a hostcell comprising a vector which comprises the appropriate encodingnucleic acid molecule under conditions suitable for expression of thePRO polypeptide and recovering the PRO polypeptide from the cellculture.

Another aspect the invention provides an isolated PRO polypeptide whichis either transmembrane domain-deleted or transmembranedomain-inactivated. Processes for producing the same are also hereindescribed, wherein those processes comprise culturing a host cellcomprising a vector which comprises the appropriate encoding nucleicacid molecule under conditions suitable for expression of the PROpolypeptide and recovering the PRO polypeptide from the cell culture.

In yet another embodiment, the invention concerns agonists andantagonists of a native PRO polypeptide as defined herein. In aparticular embodiment, the agonist or antagonist is an anti-PRO antibodyor a small molecule.

In a further embodiment, the invention concerns a method of identifyingagonists or antagonists to a PRO polypeptide which comprise contactingthe PRO polypeptide with a candidate molecule and monitoring abiological activity mediated by said PRO polypeptide. Preferably, thePRO polypeptide is a native PRO polypeptide.

In a still further embodiment, the invention concerns a composition ofmatter comprising a PRO polypeptide, or an agonist or antagonist of aPRO polypeptide as herein described, or an anti-PRO antibody, incombination with a carrier. Optionally, the carrier is apharmaceutically acceptable carrier.

Another embodiment of the present invention is directed to the use of aPRO polypeptide, or an agonist or antagonist thereof as hereinbeforedescribed, or an anti-PRO antibody, for the preparation of a medicamentuseful in the treatment of a condition which is responsive to the PROpolypeptide, an agonist or antagonist thereof or an anti-PRO antibody.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a nucleotide sequence (SEQ ID NO:1) of a native sequencePRO281 (UNQ244) cDNA, wherein SEQ ID NO:1 is a clone designated hereinas “DNA16422-1209”.

FIG. 2 shows the amino acid sequence (SEQ ID NO:2) derived from thecoding sequence of SEQ ID NO:1 shown in FIG. 1.

FIG. 3 shows a nucleotide sequence (SEQ ID NO:5) of a native sequencePRO276 (UNQ243) cDNA, wherein SEQ ID NO:5 is a clone designated hereinas “DNA16435-1208”.

FIG. 4 shows the amino acid sequence (SEQ ID NO:6) derived from thecoding sequence of SEQ ID NO:5 shown in FIG. 3.

FIG. 5 shows a nucleotide sequence (SEQ ID NO:7) of a native sequencePRO189 (UNQ163) cDNA, wherein SEQ ID NO:7 is a clone designated hereinas “DNA21624-1391”.

FIG. 6 shows the amino acid sequence (SEQ ID NO:8) derived from thecoding sequence of SEQ ID NO:7 shown in FIG. 5.

FIG. 7 shows a nucleotide sequence designated herein as DNA14187 (SEQ IDNO:9).

FIG. 8 shows a nucleotide sequence (SEQ ID NO:13) of a native sequencePRO190 (UNQ164) cDNA, wherein SEQ ID NO:13 is a clone designated hereinas “DNA23334-1392”.

FIG. 9 shows the amino acid sequence (SEQ ID NO:14) derived from thecoding sequence of SEQ ID NO:13 shown in FIG. 8.

FIG. 10 shows a nucleotide sequence designated herein as DNA14232 (SEQID NO:15).

FIG. 11 shows a nucleotide sequence (SEQ ID NO:19) of a native sequencePRO341 (UNQ300) cDNA, wherein SEQ ID NO:19 is a clone designated hereinas “DNA26288-1239”.

FIG. 12 shows the amino acid sequence (SEQ ID NO:20) derived from thecoding sequence of SEQ ID NO:19 shown in FIG. 11.

FIG. 13 shows a nucleotide sequence designated herein as DNA12920 (SEQID NO:21).

FIG. 14 shows a nucleotide sequence (SEQ ID NO:22) of a native sequencePRO180 (UNQ154) cDNA, wherein SEQ ID NO:22 is a clone designated hereinas “DNA26843-1389”.

FIG. 15 shows the amino acid sequence (SEQ ID NO:23) derived from thecoding sequence of SEQ ID NO:22 shown in FIG. 14.

FIG. 16 shows a nucleotide sequence designated herein as DNA12922 (SEQID NO:24).

FIG. 17 shows a nucleotide sequence (SEQ ID NO:27) of a native sequencePRO194 (UNQ168) cDNA, wherein SEQ ID NO:27 is a clone designated hereinas “DNA26844-1394”.

FIG. 18 shows the amino acid sequence (SEQ ID NO:28) derived from thecoding sequence of SEQ ID NO:27 shown in FIG. 17.

FIG. 19 shows a nucleotide sequence (SEQ ID NO:29) of a native sequencePRO203 (UNQ177) cDNA, wherein SEQ ID NO:29 is a clone designated hereinas “DNA30862-1396”.

FIG. 20 shows the amino acid sequence (SEQ ID NO:30) derived from thecoding sequence of SEQ ID NO:29 shown in FIG. 19.

FIG. 21 shows a nucleotide sequence designated herein as DNA15618 (SEQID NO:31).

FIG. 22 shows a nucleotide sequence (SEQ ID NO:32) of a native sequencePRO290 (UNQ253) cDNA, wherein SEQ ID NO:32 is a clone designated hereinas “DNA35680-1212”.

FIG. 23 shows the amino acid sequence (SEQ ID NO:33) derived from thecoding sequence of SEQ ID NO:32 shown in FIG. 22.

FIG. 24 shows a nucleotide sequence (SEQ ID NO:35) of a native sequencePRO874 (UNQ441) cDNA, wherein SEQ ID NO:35 is a clone designated hereinas “DNA40621-1440”.

FIG. 25 shows the amino acid sequence (SEQ ID NO:36) derived from thecoding sequence of SEQ ID NO:35 shown in FIG. 24.

FIG. 26 shows a nucleotide sequence (SEQ ID NO:40) of a native sequencePRO710 (UNQ374) cDNA, wherein SEQ ID NO:40 is a clone designated hereinas “DNA44161-1434”.

FIG. 27 shows the amino acid sequence (SEQ ID NO:41) derived from thecoding sequence of SEQ ID NO:40 shown in FIG. 26.

FIG. 28 shows a nucleotide sequence designated herein as DNA38190 (SEQID NO:42).

FIG. 29 shows a nucleotide sequence (SEQ ID NO:46) of a native sequencePRO1151 (UNQ581) cDNA, wherein SEQ ID NO:46 is a clone designated hereinas “DNA44694-1500”.

FIG. 30 shows the amino acid sequence (SEQ ID NO:47) derived from thecoding sequence of SEQ ID NO:46 shown in FIG. 29.

FIG. 31 shows a nucleotide sequence (SEQ ID NO:51) of a native sequencePRO1282 (UNQ652) cDNA, wherein SEQ ID NO:51 is a clone designated hereinas “DNA45495-1550”.

FIG. 32 shows the amino acid sequence (SEQ ID NO:52) derived from thecoding sequence of SEQ ID NO:51 shown in FIG. 31.

FIG. 33 shows a nucleotide sequence (SEQ ID NO:56) of a native sequencePRO358 cDNA, wherein SEQ ID NO:56 is a clone designated herein as“DNA47361-1154.

FIG. 34 shows the amino acid sequence (SEQ ID NO:57) derived from thecoding sequence of SEQ ID NO:56 shown in FIG. 33.

FIG. 35 shows a nucleotide sequence (SEQ ID NO:61) of a native sequencePRO1310 cDNA, wherein SEQ ID NO:61 is a clone designated herein as“DNA47394-1572.

FIG. 36 shows the amino acid sequence (SEQ ID NO:62) derived from thecoding sequence of SEQ ID NO:61 shown in FIG. 35.

FIG. 37 shows a nucleotide sequence (SEQ ID NO:66) of a native sequencePRO698 (UNQ362) cDNA, wherein SEQ ID NO:66 is a clone designated hereinas “DNA48320-1433”.

FIG. 38 shows the amino acid sequence (SEQ ID NO:67) derived from thecoding sequence of SEQ ID NO:66 shown in FIG. 37.

FIG. 39 shows a nucleotide sequence designated herein as DNA39906 (SEQID NO:68).

FIG. 40 shows a nucleotide sequence (SEQ ID NO:72) of a native sequencePRO732 (UNQ396) cDNA, wherein SEQ ID NO:72 is a clone designated hereinas “DNA48334-1435”.

FIG. 41 shows the amino acid sequence (SEQ ID NO:73) derived from thecoding sequence of SEQ ID NO:72 shown in FIG. 40.

FIG. 42 shows a nucleotide sequence designated herein as DNA20239 (SEQID NO:74).

FIG. 43 shows a nucleotide sequence designated herein as DNA38050 (SEQID NO:75).

FIG. 44 shows a nucleotide sequence designated herein as DNA40683 (SEQID NO:76).

FIG. 45 shows a nucleotide sequence designated herein as DNA42580 (SEQID NO:77).

FIG. 46 shows a nucleotide sequence (SEQ ID NO:83) of a native sequencePRO1120 (UNQ559) cDNA, wherein SEQ ID NO:83 is a clone designated hereinas “DNA48606-1479”.

FIG. 47 shows the amino acid sequence (SEQ ID NO:84) derived from thecoding sequence of SEQ ID NO:83 shown in FIG. 46.

FIG. 48 shows a nucleotide sequence (SEQ ID NO:94) of a native sequencePRO537 (UNQ338) cDNA, wherein SEQ ID NO:94 is a clone designated hereinas “DNA49141-1431”.

FIG. 49 shows the amino acid sequence (SEQ ID NO:95) derived from thecoding sequence of SEQ ID NO:94 shown in FIG. 48.

FIG. 50 shows a nucleotide sequence (SEQ ID NO:96) of a native sequencePRO536 (UNQ337) cDNA, wherein SEQ ID NO:96 is a clone designated hereinas “DNA49142-1430”.

FIG. 51 shows the amino acid sequence (SEQ ID NO:97) derived from thecoding sequence of SEQ ID NO:96 shown in FIG. 50.

FIG. 52 shows a nucleotide sequence (SEQ ID NO:98) of a native sequencePRO535 (UNQ336) cDNA, wherein SEQ ID NO:98 is a clone designated hereinas “DNA49143-1429”.

FIG. 53 shows the amino acid sequence (SEQ ID NO:99) derived from thecoding sequence of SEQ ID NO:98 shown in FIG. 52.

FIG. 54 shows a nucleotide sequence designated herein as DNA30861 (SEQID NO:100).

FIG. 55 shows a nucleotide sequence designated herein as DNA36351 (SEQID NO:101).

FIG. 56 shows a nucleotide sequence (SEQ ID NO:102) of a native sequencePRO718 (UNQ386) cDNA, wherein SEQ ID NO:102 is a clone designated hereinas “DNA49647-1398”.

FIG. 57 shows the amino acid sequence (SEQ ID NO:103) derived from thecoding sequence of SEQ ID NO:102 shown in FIG. 56.

FIG. 58 shows a nucleotide sequence designated herein as DNA15386 (SEQID NO:104).

FIG. 59 shows a nucleotide sequence designated herein as DNA16630 (SEQID NO:105).

FIG. 60 shows a nucleotide sequence designated herein as DNA16829 (SEQID NO:106).

FIG. 61 shows a nucleotide sequence designated herein as DNA28357 (SEQID NO:107).

FIG. 62 shows a nucleotide sequence designated herein as DNA43512 (SEQID NO:108).

FIG. 63 shows a nucleotide sequence (SEQ ID NO:112) of a native sequencePRO872 (UNQ439) cDNA, wherein SEQ ID NO:112 is a clone designated hereinas “DNA49819-1439”.

FIG. 64 shows the amino acid sequence (SEQ ID NO:113) derived from thecoding sequence of SEQ ID NO:112 shown in FIG. 63.

FIG. 65 shows a nucleotide sequence (SEQ ID NO:114) of a native sequencePRO1063 (UNQ128) cDNA, wherein SEQ ID NO:114 is a clone designatedherein as “DNA49820-1427”.

FIG. 66 shows the amino acid sequence (SEQ ID NO:115) derived from thecoding sequence of SEQ ID NO:114 shown in FIG. 65.

FIG. 67 shows a nucleotide sequence (SEQ ID NO:116) of a native sequencePRO619 (UNQ355) cDNA, wherein SEQ ID NO:116 is a clone designated hereinas “DNA49821-1562”.

FIG. 68 shows the amino acid sequence (SEQ ID NO:117) derived from thecoding sequence of SEQ ID NO:116 shown in FIG. 67.

FIG. 69 shows a nucleotide sequence (SEQ ID NO:118) of a native sequencePRO943 (UNQ480) cDNA, wherein SEQ ID NO:118 is a clone designated hereinas “DNA52192-1369”.

FIG. 70 shows the amino acid sequence (SEQ ID NO:119) derived from thecoding sequence of SEQ ID NO:118 shown in FIG. 69.

FIG. 71 shows a nucleotide sequence (SEQ ID NO:123) of a native sequencePRO1188 (UNQ602) cDNA, wherein SEQ ID NO:123 is a clone designatedherein as “DNA52598-1518”.

FIG. 72 shows the amino acid sequence (SEQ ID NO:124) derived from thecoding sequence of SEQ ID NO:123 shown in FIG. 71.

FIG. 73 shows a nucleotide sequence (SEQ ID NO:128) of a native sequencePRO1133 (UNQ571) cDNA, wherein SEQ ID NO:128 is a clone designatedherein as “DNA53913-1490”.

FIG. 74 shows the amino acid sequence (SEQ ID NO:129) derived from thecoding sequence of SEQ ID NO:128 shown in FIG. 73.

FIG. 75 shows a nucleotide sequence (SEQ ID NO:134) of a native sequencePRO784 (UNQ459) cDNA, wherein SEQ ID NO:134 is a clone designated hereinas “DNA53978-1443”.

FIG. 76 shows the amino acid sequence (SEQ ID NO:135) derived from thecoding sequence of SEQ ID NO:134 shown in FIG. 75.

FIG. 77 shows a nucleotide sequence designated herein as DNA44661 (SEQID NO:136).

FIG. 78 shows a nucleotide sequence (SEQ ID NO:137) of a native sequencePRO783 (UNQ458) cDNA, wherein SEQ ID NO:137 is a clone designated hereinas “DNA53996-1442”.

FIG. 79 shows the amino acid sequence (SEQ ID NO:138) derived from thecoding sequence of SEQ ID NO:137 shown in FIG. 78.

FIG. 80 shows a nucleotide sequence designated herein as DNA45201 (SEQID NO:139).

FIG. 81 shows a nucleotide sequence designated herein as DNA 14575 (SEQID NO:140).

FIG. 82 shows a nucleotide sequence (SEQ ID NO:145) of a native sequencePRO820 (UNQ503) cDNA, wherein SEQ ID NO:145 is a clone designated hereinas “DNA56041-1416”.

FIG. 83 shows the amino acid sequence (SEQ ID NO:146) derived from thecoding sequence of SEQ ID NO:145 shown in FIG. 82.

FIG. 84 shows a nucleotide sequence (SEQ ID NO:147) of a native sequencePRO1080 (UNQ537) cDNA, wherein SEQ ID NO:147 is a clone designatedherein as “DNA56047-1456”.

FIG. 85 shows the amino acid sequence (SEQ ID NO:148) derived from thecoding sequence of SEQ ID NO:147 shown in FIG. 84.

FIG. 86 shows a nucleotide sequence designated herein as DNA36527 (SEQID NO:149).

FIG. 87 shows a nucleotide sequence (SEQ ID NO:150) of a native sequencePRO1079 (UNQ536) cDNA, wherein SEQ ID NO:150 is a clone designatedherein as “DNA56050-1455”.

FIG. 88 shows the amino acid sequence (SEQ ID NO:151) derived from thecoding sequence of SEQ ID NO:150 shown in FIG. 87.

FIG. 89 shows a nucleotide sequence (SEQ ID NO:152) of a native sequencePRO793 (UNQ432) cDNA, wherein SEQ ID NO:152 is a clone designated hereinas “DNA56110-1437”.

FIG. 90 shows the amino acid sequence (SEQ ID NO:153) derived from thecoding sequence of SEQ ID NO:152 shown in FIG. 89.

FIG. 91 shows a nucleotide sequence designated herein as DNA50177 (SEQID NO:154).

FIG. 92 shows a nucleotide sequence (SEQ ID NO:155) of a native sequencePRO1016 (UNQ499) cDNA, wherein SEQ ID NO:155 is a clone designatedherein as “DNA56113-1378”.

FIG. 93 shows the amino acid sequence (SEQ ID NO:156) derived from thecoding sequence of SEQ ID NO:155 shown in FIG. 92.

FIG. 94 shows a nucleotide sequence (SEQ ID NO:157) of a native sequencePRO1013 (UNQ496) cDNA, wherein SEQ ID NO:157 is a clone designatedherein as “DNA56410-1414”.

FIG. 95 shows the amino acid sequence (SEQ ID NO:158) derived from thecoding sequence of SEQ ID NO:157 shown in FIG. 94.

FIG. 96 shows a nucleotide sequence (SEQ ID NO:159) of a native sequencePRO937 (UNQ474) cDNA, wherein SEQ ID NO:159 is a clone designated hereinas “DNA56436-1448”.

FIG. 97 shows the amino acid sequence (SEQ ID NO:160) derived from thecoding sequence of SEQ ID NO:159 shown in FIG. 96.

FIG. 98 shows a nucleotide sequence (SEQ ID NO:164) of a native sequencePRO842 (UNQ473) cDNA, wherein SEQ ID NO:164 is a clone designated hereinas “DNA56855-1447”.

FIG. 99 shows the amino acid sequence (SEQ ID NO:165) derived from thecoding sequence of SEQ ID NO:164 shown in FIG. 98.

FIG. 100 shows a nucleotide sequence (SEQ ID NO:166) of a nativesequence PRO839 (UNQ472) cDNA, wherein SEQ ID NO:166 is a clonedesignated herein as “DNA56859-1445”.

FIG. 101 shows the amino acid sequence (SEQ ID NO:167) derived from thecoding sequence of SEQ ID NO:166 shown in FIG. 100.

FIG. 102 shows a nucleotide sequence (SEQ ID NO:168) of a nativesequence PRO1180 (UNQ594) cDNA, wherein SEQ ID NO:168 is a clonedesignated herein as “DNA56860-1510”.

FIG. 103 shows the amino acid sequence (SEQ ID NO:169) derived from thecoding sequence of SEQ ID NO:168 shown in FIG. 102.

FIG. 104 shows a nucleotide sequence (SEQ ID NO:170) of a nativesequence PRO1134 (UNQ572) cDNA, wherein SEQ ID NO:170 is a clonedesignated herein as “DNA56865-1491”.

FIG. 105 shows the amino acid sequence (SEQ ID NO:171) derived from thecoding sequence of SEQ ID NO:170 shown in FIG. 104.

FIG. 106 shows a nucleotide sequence designated herein as DNA52352 (SEQID NO:172).

FIG. 107 shows a nucleotide sequence designated herein as DNA55725 (SEQID NO:173).

FIG. 108 shows a nucleotide sequence (SEQ ID NO:174) of a nativesequence PRO830 (UNQ470) cDNA, wherein SEQ ID NO:174 is a clonedesignated herein as “DNA56866-1342”.

FIG. 109 shows the amino acid sequence (SEQ ID NO:175) derived from thecoding sequence of SEQ ID NO:174 shown in FIG. 108.

FIG. 110 shows a nucleotide sequence (SEQ ID NO:176) of a nativesequence PRO1115 (UNQ558) cDNA, wherein SEQ ID NO:176 is a clonedesignated herein as “DNA56868-1478”.

FIG. 111 shows the amino acid sequence (SEQ ID NO:177) derived from thecoding sequence of SEQ ID NO:176 shown in FIG. 110.

FIG. 112 shows a nucleotide sequence (SEQ ID NO:178) of a nativesequence PRO1277 (UNQ647) cDNA, wherein SEQ ID NO:178 is a clonedesignated herein as “DNA56869-1545”.

FIG. 113 shows the amino acid sequence (SEQ ID NO:179) derived from thecoding sequence of SEQ ID NO:178 shown in FIG. 112.

FIG. 114 shows a nucleotide sequence (SEQ ID NO:180) of a nativesequence PRO1135 (UNQ573) cDNA, wherein SEQ ID NO:180 is a clonedesignated herein as “DNA56870-1492”.

FIG. 115 shows the amino acid sequence (SEQ ID NO:181) derived from thecoding sequence of SEQ ID NO:180 shown in FIG. 114.

FIG. 116 shows a nucleotide sequence (SEQ ID NO:182) of a nativesequence PRO1114 (UNQ557) cDNA, wherein SEQ ID NO:182 is a clonedesignated herein as “DNA57033-1403”.

FIG. 117 shows the amino acid sequence (SEQ ID NO:183) derived from thecoding sequence of SEQ ID NO:182 shown in FIG. 116.

FIG. 118 shows a nucleotide sequence designated herein as DNA48466 (SEQID NO:184).

FIG. 119 shows a nucleotide sequence (SEQ ID NO:188) of a nativesequence PRO828 (UNQ469) cDNA, wherein SEQ ID NO:188 is a clonedesignated herein as “DNA57037-1444”.

FIG. 120 shows the amino acid sequence (SEQ ID NO:189) derived from thecoding sequence of SEQ ID NO:188 shown in FIG. 119.

FIG. 121 shows a nucleotide sequence (SEQ ID NO:193) of a nativesequence PRO1009 (UNQ493) cDNA, wherein SEQ ID NO:193 is a clonedesignated herein as “DNA57129-1413”.

FIG. 122 shows the amino acid sequence (SEQ ID NO:194) derived from thecoding sequence of SEQ ID NO:193 shown in FIG. 121.

FIG. 123 shows a nucleotide sequence designated herein as DNA50853 (SEQID NO:195).

FIG. 124 shows a nucleotide sequence (SEQ ID NO:196) of a nativesequence PRO1007 (UNQ491) cDNA, wherein SEQ ID NO:196 is a clonedesignated herein as “DNA57690-1374”.

FIG. 125 shows the amino acid sequence (SEQ ID NO:197) derived from thecoding sequence of SEQ ID NO:196 shown in FIG. 124.

FIG. 126 shows a nucleotide sequence (SEQ ID NO:198) of a nativesequence PRO1056 (UNQ521) cDNA, wherein SEQ ID NO:198 is a clonedesignated herein as “DNA57693-1424”.

FIG. 127 shows the amino acid sequence (SEQ ID NO:199) derived from thecoding sequence of SEQ ID NO:198 shown in FIG. 126.

FIG. 128 shows a nucleotide sequence (SEQ ID NO:200) of a nativesequence PRO826 (UNQ467) cDNA, wherein SEQ ID NO:200 is a clonedesignated herein as “DNA57694-1341”.

FIG. 129 shows the amino acid sequence (SEQ ID NO:201) derived from thecoding sequence of SEQ ID NO:200 shown in FIG. 128.

FIG. 130 shows a nucleotide sequence (SEQ ID NO:202) of a nativesequence PRO819 (UNQ466) cDNA, wherein SEQ ID NO:202 is a clonedesignated herein as “DNA57695-1340”.

FIG. 131 shows the amino acid sequence (SEQ ID NO:203) derived from thecoding sequence of SEQ ID NO:202 shown in FIG. 130.

FIG. 132 shows a nucleotide sequence (SEQ ID NO:204) of a nativesequence PRO1006 (UNQ490) cDNA, wherein SEQ ID NO:204 is a clonedesignated herein as “DNA57699-1412”.

FIG. 133 shows the amino acid sequence (SEQ ID NO:205) derived from thecoding sequence of SEQ ID NO:204 shown in FIG. 132.

FIG. 134 shows a nucleotide sequence (SEQ ID NO:206) of a nativesequence PRO1112 (UNQ555) cDNA, wherein SEQ ID NO:206 is a clonedesignated herein as “DNA57702-1476”.

FIG. 135 shows the amino acid sequence (SEQ ID NO:207) derived from thecoding sequence of SEQ ID NO:206 shown in FIG. 134.

FIG. 136 shows a nucleotide sequence (SEQ ID NO:208) of a nativesequence PRO1074 (UNQ531) cDNA, wherein SEQ ID NO:208 is a clonedesignated herein as “DNA57704-1452”.

FIG. 137 shows the amino acid sequence (SEQ ID NO:209) derived from thecoding sequence of SEQ ID NO:208 shown in FIG. 136.

FIG. 138 shows a nucleotide sequence (SEQ ID NO:210) of a nativesequence PRO1005 (UNQ489) cDNA, wherein SEQ ID NO:210 is a clonedesignated herein as “DNA57708-1005”.

FIG. 139 shows the amino acid sequence (SEQ ID NO:211) derived from thecoding sequence of SEQ ID NO:210 shown in FIG. 138.

FIG. 140 shows a nucleotide sequence (SEQ ID NO:212) of a nativesequence PRO1073 (UNQ530) cDNA, wherein SEQ ID NO:212 is a clonedesignated herein as “DNA57710-1451”.

FIG. 141 shows the amino acid sequence (SEQ ID NO:213) derived from thecoding sequence of SEQ ID NO:212 shown in FIG. 140.

FIG. 142 shows a nucleotide sequence designated herein as DNA55938 (SEQID NO:214).

FIG. 143 shows a nucleotide sequence (SEQ ID NO:215) of a nativesequence PRO1152 (UNQ582) cDNA, wherein SEQ ID NO:215 is a clonedesignated herein as “DNA57711-1501”.

FIG. 144 shows the amino acid sequence (SEQ ID NO:216) derived from thecoding sequence of SEQ ID NO:215 shown in FIG. 143.

FIG. 145 shows a nucleotide sequence designated herein as DNA55807 (SEQID NO:217).

FIG. 146 shows a nucleotide sequence (SEQ ID NO:218) of a nativesequence PRO1136 (UNQ574) cDNA, wherein SEQ ID NO:218 is a clonedesignated herein as “DNA57827-1493”.

FIG. 147 shows the amino acid sequence (SEQ ID NO:219) derived from thecoding sequence of SEQ ID NO:218 shown in FIG. 146.

FIG. 148 shows a nucleotide sequence (SEQ ID NO:220) of a nativesequence PRO813 (UNQ465) cDNA, wherein SEQ ID NO:220 is a clonedesignated herein as “DNA57834-1339”.

FIG. 149 shows the amino acid sequence (SEQ ID NO:221) derived from thecoding sequence of SEQ ID NO:220 shown in FIG. 148.

FIG. 150 shows a nucleotide sequence (SEQ ID NO:222) of a nativesequence PRO809 (UNQ464) cDNA, wherein SEQ ID NO:222 is a clonedesignated herein as “DNA57836-1338”.

FIG. 151 shows the amino acid sequence (SEQ ID NO:223) derived from thecoding sequence of SEQ ID NO:222 shown in FIG. 150.

FIG. 152 shows a nucleotide sequence (SEQ ID NO:224) of a nativesequence PRO791 (UNQ463) cDNA, wherein SEQ ID NO:224 is a clonedesignated herein as “DNA57838-1337”.

FIG. 153 shows the amino acid sequence (SEQ ID NO:225) derived from thecoding sequence of SEQ ID NO:224 shown in FIG. 152.

FIG. 154 shows a nucleotide sequence (SEQ ID NO:226) of a nativesequence PRO1004 (UNQ488) cDNA, wherein SEQ ID NO:226 is a clonedesignated herein as “DNA57844-1410”.

FIG. 155 shows the amino acid sequence (SEQ ID NO:227) derived from thecoding sequence of SEQ ID NO:226 shown in FIG. 154.

FIG. 156 shows a nucleotide sequence (SEQ ID NO:228) of a nativesequence PRO1111 (UNQ554) cDNA, wherein SEQ ID NO:228 is a clonedesignated herein as “DNA58721-1475”.

FIG. 157 shows the amino acid sequence (SEQ ID NO:229) derived from thecoding sequence of SEQ ID NO:228 shown in FIG. 156.

FIG. 158 shows a nucleotide sequence (SEQ ID NO:230) of a nativesequence PRO1344 (UNQ699) cDNA, wherein SEQ ID NO:230 is a clonedesignated herein as “DNA58723-1588”.

FIG. 159 shows the amino acid sequence (SEQ ID NO:231) derived from thecoding sequence of SEQ ID NO:230 shown in FIG. 158.

FIG. 160 shows a nucleotide sequence (SEQ ID NO:235) of a nativesequence PRO1109 (UNQ552) cDNA, wherein SEQ ID NO:235 is a clonedesignated herein as “DNA58737-1473”.

FIG. 161 shows the amino acid sequence (SEQ ID NO:236) derived from thecoding sequence of SEQ ID NO:235 shown in FIG. 160.

FIG. 162 shows a nucleotide sequence (SEQ ID NO:240) of a nativesequence PRO1383 (UNQ719) cDNA, wherein SEQ ID NO:240 is a clonedesignated herein as “DNA58743-1609”.

FIG. 163 shows the amino acid sequence (SEQ ID NO:241) derived from thecoding sequence of SEQ ID NO:240 shown in FIG. 162.

FIG. 164 shows a nucleotide sequence (SEQ ID NO:245) of a nativesequence PRO1003 (UNQ487) cDNA, wherein SEQ ID NO:245 is a clonedesignated herein as “DNA58846-1409”.

FIG. 165 shows the amino acid sequence (SEQ ID NO:246) derived from thecoding sequence of SEQ ID NO:245 shown in FIG. 164.

FIG. 166 shows a nucleotide sequence (SEQ ID NO:247) of a nativesequence PRO1108 (UNQ551) cDNA, wherein SEQ ID NO:247 is a clonedesignated herein as “DNA58848-1472”.

FIG. 167 shows the amino acid sequence (SEQ ID NO:248) derived from thecoding sequence of SEQ ID NO:247 shown in FIG. 166.

FIG. 168 shows a nucleotide sequence (SEQ ID NO:249) of a nativesequence PRO1137 (UNQ575) cDNA, wherein SEQ ID NO:249 is a clonedesignated herein as “DNA58849-1494”.

FIG. 169 shows the amino acid sequence (SEQ ID NO:250) derived from thecoding sequence of SEQ ID NO:249 shown in FIG. 168.

FIG. 170 shows a nucleotide sequence (SEQ ID NO:252) of a nativesequence PRO1138 (UNQ576) cDNA, wherein SEQ ID NO:252 is a clonedesignated herein as “DNA58850-1495”.

FIG. 171 shows the amino acid sequence (SEQ ID NO:253) derived from thecoding sequence of SEQ ID NO:252 shown in FIG. 170.

FIG. 172 shows a nucleotide sequence designated herein as DNA49140 (SEQID NO:254).

FIG. 173 shows a nucleotide sequence (SEQ ID NO:255) of a nativesequence PRO1054 (UNQ519) cDNA, wherein SEQ ID NO:255 is a clonedesignated herein as “DNA58853-1423”.

FIG. 174 shows the amino acid sequence (SEQ ID NO:256) derived from thecoding sequence of SEQ ID NO:255 shown in FIG. 173.

FIG. 175 shows a nucleotide sequence (SEQ ID NO:257) of a nativesequence PRO994 (UNQ518) cDNA, wherein SEQ ID NO:257 is a clonedesignated herein as “DNA58855-1422”.

FIG. 176 shows the amino acid sequence (SEQ ID NO:258) derived from thecoding sequence of SEQ ID NO:257 shown in FIG. 175.

FIG. 177 shows a nucleotide sequence (SEQ ID NO:259) of a nativesequence PRO812 (UNQ517) cDNA, wherein SEQ ID NO:259 is a clonedesignated herein as “DNA59205-1421”.

FIG. 178 shows the amino acid sequence (SEQ ID NO:260) derived from thecoding sequence of SEQ ID NO:259 shown in FIG. 177.

FIG. 179 shows a nucleotide sequence (SEQ ID NO:261) of a nativesequence PRO1069 (UNQ526) cDNA, wherein SEQ ID NO:261 is a clonedesignated herein as “DNA59211-1450”.

FIG. 180 shows the amino acid sequence (SEQ ID NO:262) derived from thecoding sequence of SEQ ID NO:261 shown in FIG. 179.

FIG. 181 shows a nucleotide sequence (SEQ ID NO:263) of a nativesequence PRO1129 (UNQ568) cDNA, wherein SEQ ID NO:263 is a clonedesignated herein as “DNA59213-1487”.

FIG. 182 shows the amino acid sequence (SEQ ID NO:264) derived from thecoding sequence of SEQ ID NO:263 shown in FIG. 181.

FIG. 183 shows a nucleotide sequence (SEQ ID NO:265) of a nativesequence PRO1068 (UNQ525) cDNA, wherein SEQ ID NO:265 is a clonedesignated herein as “DNA59214-1449”.

FIG. 184 shows the amino acid sequence (SEQ ID NO:266) derived from thecoding sequence of SEQ ID NO:265 shown in FIG. 183.

FIG. 185 shows a nucleotide sequence (SEQ ID NO:267) of a nativesequence PRO1066 (UNQ524) cDNA, wherein SEQ ID NO:267 is a clonedesignated herein as “DNA59215-1425”.

FIG. 186 shows the amino acid sequence (SEQ ID NO:268) derived from thecoding sequence of SEQ ID NO:267 shown in FIG. 185.

FIG. 187 shows a nucleotide sequence (SEQ ID NO:269) of a nativesequence PRO1184 (UNQ598) cDNA, wherein SEQ ID NO:269 is a clonedesignated herein as “DNA59220-1514”.

FIG. 188 shows the amino acid sequence (SEQ ID NO:270) derived from thecoding sequence of SEQ ID NO:269 shown in FIG. 187.

FIG. 189 shows a nucleotide sequence (SEQ ID NO:271) of a nativesequence PRO1360 (UNQ709) cDNA, wherein SEQ ID NO:271 is a clonedesignated herein as “DNA59488-1603”.

FIG. 190 shows the amino acid sequence (SEQ ID NO:272) derived from thecoding sequence of SEQ ID NO:271 shown in FIG. 189.

FIG. 191 shows a nucleotide sequence (SEQ ID NO:273) of a nativesequence PRO1029 (UNQ514) cDNA, wherein SEQ ID NO:273 is a clonedesignated herein as “DNA59493-1420”.

FIG. 192 shows the amino acid sequence (SEQ ID NO:274) derived from thecoding sequence of SEQ ID NO:273 shown in FIG. 191.

FIG. 193 shows a nucleotide sequence (SEQ ID NO:275) of a nativesequence PRO1139 (UNQ577) cDNA, wherein SEQ ID NO:275 is a clonedesignated herein as “DNA59497-1496”.

FIG. 194 shows the amino acid sequence (SEQ ID NO:276) derived from thecoding sequence of SEQ ID NO:275 shown in FIG. 193.

FIG. 195 shows a nucleotide sequence (SEQ ID NO:277) of a nativesequence PRO1309 (UNQ675) cDNA, wherein SEQ ID NO:277 is a clonedesignated herein as “DNA59588-1571”.

FIG. 196 shows the amino acid sequence (SEQ ID NO:278) derived from thecoding sequence of SEQ ID NO:277 shown in FIG. 195.

FIG. 197 shows a nucleotide sequence (SEQ ID NO:280) of a nativesequence PRO1028 (UNQ513) cDNA, wherein SEQ ID NO:280 is a clonedesignated herein as “DNA59603-1419”.

FIG. 198 shows the amino acid sequence (SEQ ID NO:281) derived from thecoding sequence of SEQ ID NO:280 shown in FIG. 197.

FIG. 199 shows a nucleotide sequence (SEQ ID NO:282) of a nativesequence PRO1027 (UNQ512) cDNA, wherein SEQ ID NO:282 is a clonedesignated herein as “DNA59605-1418”.

FIG. 200 shows the amino acid sequence (SEQ ID NO:283) derived from thecoding sequence of SEQ ID NO:282 shown in FIG. 199.

FIG. 201 shows a nucleotide sequence (SEQ ID NO:284) of a nativesequence PRO1107 (UNQ550) cDNA, wherein SEQ ID NO:284 is a clonedesignated herein as “DNA59606-1471”.

FIG. 202 shows the amino acid sequence (SEQ ID NO:285) derived from thecoding sequence of SEQ ID NO:284 shown in FIG. 201.

FIG. 203 shows a nucleotide sequence (SEQ ID NO:286) of a nativesequence PRO1140 (UNQ578) cDNA, wherein SEQ ID NO:286 is a clonedesignated herein as “DNA59607-1497”.

FIG. 204 shows the amino acid sequence (SEQ ID NO:287) derived from thecoding sequence of SEQ ID NO:286 shown in FIG. 203.

FIG. 205 shows a nucleotide sequence (SEQ ID NO:288) of a nativesequence PRO1106 (UNQ549) cDNA, wherein SEQ ID NO:288 is a clonedesignated herein as “DNA59609-1470”.

FIG. 206 shows the amino acid sequence (SEQ ID NO:289) derived from thecoding sequence of SEQ ID NO:288 shown in FIG. 205.

FIG. 207 shows a nucleotide sequence (SEQ ID NO:290) of a nativesequence PRO1291 (UNQ659) cDNA, wherein SEQ ID NO:290 is a clonedesignated herein as “DNA59610-1556”.

FIG. 208 shows the amino acid sequence (SEQ ID NO:291) derived from thecoding sequence of SEQ ID NO:290 shown in FIG. 207.

FIG. 209 shows a nucleotide sequence (SEQ ID NO:292) of a nativesequence PRO1105 (UNQ548) cDNA, wherein SEQ ID NO:292 is a clonedesignated herein as “DNA59612-1466”.

FIG. 210 shows the amino acid sequence (SEQ ID NO:293) derived from thecoding sequence of SEQ ID NO:292 shown in FIG. 209.

FIG. 211 shows a nucleotide sequence (SEQ ID NO:294) of a nativesequence PRO511 (UNQ511) cDNA, wherein SEQ ID NO:294 is a clonedesignated herein as “DNA59613-1417”.

FIG. 212 shows the amino acid sequence (SEQ ID NO:295) derived from thecoding sequence of SEQ ID NO:294 shown in FIG. 211.

FIG. 213 shows a nucleotide sequence (SEQ ID NO:296) of a nativesequence PRO1104 (UNQ547) cDNA, wherein SEQ ID NO:296 is a clonedesignated herein as “DNA59616-1465”.

FIG. 214 shows the amino acid sequence (SEQ ID NO:297) derived from thecoding sequence of SEQ ID NO:296 shown in FIG. 213.

FIG. 215 shows a nucleotide sequence (SEQ ID NO:298) of a nativesequence PRO1100 (UNQ546) cDNA, wherein SEQ ID NO:298 is a clonedesignated herein as “DNA59619-1464”.

FIG. 216 shows the amino acid sequence (SEQ ID NO:299) derived from thecoding sequence of SEQ ID NO:298 shown in FIG. 215.

FIG. 217 shows a nucleotide sequence (SEQ ID NO:300) of a nativesequence PRO836 (UNQ545) cDNA, wherein SEQ ID NO:300 is a clonedesignated herein as “DNA59620-1463”.

FIG. 218 shows the amino acid sequence (SEQ ID NO:301) derived from thecoding sequence of SEQ ID NO:300 shown in FIG. 217.

FIG. 219 shows a nucleotide sequence (SEQ ID NO:302) of a nativesequence PRO1141 (UNQ579) cDNA, wherein SEQ ID NO:302 is a clonedesignated herein as “DNA59625-1498”.

FIG. 220 shows the amino acid sequence (SEQ ID NO:303) derived from thecoding sequence of SEQ ID NO:302 shown in FIG. 219.

FIG. 221 shows a nucleotide sequence designated herein as DNA33128 (SEQID NO:304).

FIG. 222 shows a nucleotide sequence designated herein as DNA34256 (SEQID NO:305).

FIG. 223 shows a nucleotide sequence designated herein as DNA47941 (SEQID NO:306).

FIG. 224 shows a nucleotide sequence designated herein as DNA54389 (SEQID NO:307).

FIG. 225 shows a nucleotide sequence (SEQ ID NO:308) of a nativesequence PRO1132 (UNQ570) cDNA, wherein SEQ ID NO:308 is a clonedesignated herein as “DNA59767-1489”.

FIG. 226 shows the amino acid sequence (SEQ ID NO:309) derived from thecoding sequence of SEQ ID NO:308 shown in FIG. 225.

FIG. 227 shows a nucleotide sequence (SEQ ID NO:313) of a nativesequence PRO1346 cDNA, wherein SEQ ID NO:313 is a clone designatedherein as “DNA59776-1600”.

FIG. 228 shows the amino acid sequence (SEQ ID NO:314) derived from thecoding sequence of SEQ ID NO:313 shown in FIG. 227.

FIG. 229 shows a nucleotide sequence (SEQ ID NO:318) of a nativesequence PRO1131 (UNQ569) cDNA, wherein SEQ ID NO:318 is a clonedesignated herein as “DNA59777-1480”.

FIG. 230 shows the amino acid sequence (SEQ ID NO:319) derived from thecoding sequence of SEQ ID NO:318 shown in FIG. 229.

FIG. 231 shows a nucleotide sequence designated herein as DNA43546 (SEQID NO:320).

FIG. 232 shows a nucleotide sequence (SEQ ID NO:325) of a nativesequence PRO1281 (UNQ651) cDNA, wherein SEQ ID NO:325 is a clonedesignated herein as “DNA59820-1549”.

FIG. 233 shows the amino acid sequence (SEQ ID NO:326) derived from thecoding sequence of SEQ ID NO:325 shown in FIG. 232.

FIG. 234 shows a nucleotide sequence (SEQ ID NO:333) of a nativesequence PRO1064 (UNQ111) cDNA, wherein SEQ ID NO:333 is a clonedesignated herein as “DNA59827-1426”.

FIG. 235 shows the amino acid sequence (SEQ ID NO:334) derived from thecoding sequence of SEQ ID NO:333 shown in FIG. 234.

FIG. 236 shows a nucleotide sequence designated herein as DNA45288 (SEQID NO:335).

FIG. 237 shows a nucleotide sequence (SEQ ID NO:339) of a nativesequence PRO1379 (UNQ716) cDNA, wherein SEQ ID NO:339 is a clonedesignated herein as “DNA59828-1608”.

FIG. 238 shows the amino acid sequence (SEQ ID NO:340) derived from thecoding sequence of SEQ ID NO:339 shown in FIG. 237.

FIG. 239 shows a nucleotide sequence (SEQ ID NO:344) of a nativesequence PRO844 (UNQ544) cDNA, wherein SEQ ID NO:344 is a clonedesignated herein as “DNA59838-1462”.

FIG. 240 shows the amino acid sequence (SEQ ID NO:345) derived from thecoding sequence of SEQ ID NO:344 shown in FIG. 239.

FIG. 241 shows a nucleotide sequence (SEQ ID NO:346) of a nativesequence PRO848 (UNQ543) cDNA, wherein SEQ ID NO:346 is a clonedesignated herein as “DNA59839-1461”.

FIG. 242 shows the amino acid sequence (SEQ ID NO:347) derived from thecoding sequence of SEQ ID NO:346 shown in FIG. 241.

FIG. 243 shows a nucleotide sequence (SEQ ID NO:348) of a nativesequence PRO1097 (UNQ542) cDNA, wherein SEQ ID NO:348 is a clonedesignated herein as “DNA59841-1460”.

FIG. 244 shows the amino acid sequence (SEQ ID NO:349) derived from thecoding sequence of SEQ ID NO:348 shown in FIG. 243.

FIG. 245 shows a nucleotide sequence (SEQ ID NO:350) of a nativesequence PRO1153 (UNQ583) cDNA, wherein SEQ ID NO:350 is a clonedesignated herein as “DNA59842-1502”.

FIG. 246 shows the amino acid sequence (SEQ ID NO:351) derived from thecoding sequence of SEQ ID NO:350 shown in FIG. 245.

FIG. 247 shows a nucleotide sequence (SEQ ID NO:352) of a nativesequence PRO1154 (UNQ584) cDNA, wherein SEQ ID NO:352 is a clonedesignated herein as “DNA59846-1503”.

FIG. 248 shows the amino acid sequence (SEQ ID NO:353) derived from thecoding sequence of SEQ ID NO:352 shown in FIG. 247.

FIG. 249 shows a nucleotide sequence (SEQ ID NO:354) of a nativesequence PRO1181 (UNQ595) cDNA, wherein SEQ ID NO:354 is a clonedesignated herein as “DNA59847-1511”.

FIG. 250 shows the amino acid sequence (SEQ ID NO:355) derived from thecoding sequence of SEQ ID NO:354 shown in FIG. 249.

FIG. 251 shows a nucleotide sequence (SEQ ID NO:356) of a nativesequence PRO1182 (UNQ596) cDNA, wherein SEQ ID NO:356 is a clonedesignated herein as “DNA59848-1512”.

FIG. 252 shows the amino acid sequence (SEQ ID NO:357) derived from thecoding sequence of SEQ ID NO:356 shown in FIG. 251.

FIG. 253 shows a nucleotide sequence (SEQ ID NO:358) of a nativesequence PRO1155 (UNQ585) cDNA, wherein SEQ ID NO:358 is a clonedesignated herein as “DNA59849-1504”.

FIG. 254 shows the amino acid sequence (SEQ ID NO:359) derived from thecoding sequence of SEQ ID NO:358 shown in FIG. 253.

FIG. 255 shows a nucleotide sequence (SEQ ID NO:360) of a nativesequence PRO1156 (UNQ586) cDNA, wherein SEQ ID NO:360 is a clonedesignated herein as “DNA59853-1505”.

FIG. 256 shows the amino acid sequence (SEQ ID NO:361) derived from thecoding sequence of SEQ ID NO:360 shown in FIG. 255.

FIG. 257 shows a nucleotide sequence (SEQ ID NO:362) of a nativesequence PRO1098 (UNQ541) cDNA, wherein SEQ ID NO:362 is a clonedesignated herein as “DNA59854-1459”.

FIG. 258 shows the amino acid sequence (SEQ ID NO:363) derived from thecoding sequence of SEQ ID NO:362 shown in FIG. 257.

FIG. 259 shows a nucleotide sequence (SEQ ID NO:364) of a nativesequence PRO1127 (UNQ565) cDNA, wherein SEQ ID NO:364 is a clonedesignated herein as “DNA60283-1484”.

FIG. 260 shows the amino acid sequence (SEQ ID NO:365) derived from thecoding sequence of SEQ ID NO:364 shown in FIG. 259.

FIG. 261 shows a nucleotide sequence (SEQ ID NO:366) of a nativesequence PRO1126 (UNQ564) cDNA, wherein SEQ ID NO:366 is a clonedesignated herein as “DNA60615-1483”.

FIG. 262 shows the amino acid sequence (SEQ ID NO:367) derived from thecoding sequence of SEQ ID NO:366 shown in FIG. 261.

FIG. 263 shows a nucleotide sequence (SEQ ID NO:368) of a nativesequence PRO1125 (UNQ563) cDNA, wherein SEQ ID NO:368 is a clonedesignated herein as “DNA60619-1482”.

FIG. 264 shows the amino acid sequence (SEQ ID NO:369) derived from thecoding sequence of SEQ ID NO:368 shown in FIG. 263.

FIG. 265 shows a nucleotide sequence (SEQ ID NO:370) of a nativesequence PRO1186 (UNQ600) cDNA, wherein SEQ ID NO:370 is a clonedesignated herein as “DNA60621-1516”.

FIG. 266 shows the amino acid sequence (SEQ ID NO:371) derived from thecoding sequence of SEQ ID NO:370 shown in FIG. 265.

FIG. 267 shows a nucleotide sequence (SEQ ID NO:372) of a nativesequence PRO1198 (UNQ611) cDNA, wherein SEQ ID NO:372 is a clonedesignated herein as “DNA60622-1525”.

FIG. 268 shows the amino acid sequence (SEQ ID NO:373) derived from thecoding sequence of SEQ ID NO:372 shown in FIG. 267.

FIG. 269 shows a nucleotide sequence (SEQ ID NO:374) of a nativesequence PRO1158 (UNQ588) cDNA, wherein SEQ ID NO:374 is a clonedesignated herein as “DNA60625-1507”.

FIG. 270 shows the amino acid sequence (SEQ ID NO:375) derived from thecoding sequence of SEQ ID NO:374 shown in FIG. 269.

FIG. 271 shows a nucleotide sequence (SEQ ID NO:376) of a nativesequence PRO1159 (UNQ589) cDNA, wherein SEQ ID NO:376 is a clonedesignated herein as “DNA60627-1508”.

FIG. 272 shows the amino acid sequence (SEQ ID NO:377) derived from thecoding sequence of SEQ ID NO:376 shown in FIG. 271.

FIG. 273 shows a nucleotide sequence (SEQ ID NO:378) of a nativesequence PRO1124 (UNQ562) cDNA, wherein SEQ ID NO:378 is a clonedesignated herein as “DNA60629-1481”.

FIG. 274 shows the amino acid sequence (SEQ ID NO:379) derived from thecoding sequence of SEQ ID NO:378 shown in FIG. 273.

FIG. 275 shows a nucleotide sequence (SEQ ID NO:380) of a nativesequence PRO1287 (UNQ656) cDNA, wherein SEQ ID NO:380 is a clonedesignated herein as “DNA61755-1554”.

FIG. 276 shows the amino acid sequence (SEQ ID NO:381) derived from thecoding sequence of SEQ ID NO:380 shown in FIG. 275.

FIG. 277 shows a nucleotide sequence (SEQ ID NO:386) of a nativesequence PRO1312 (UNQ678) cDNA, wherein SEQ ID NO:386 is a clonedesignated herein as “DNA61873-1574”.

FIG. 278 shows the amino acid sequence (SEQ ID NO:387) derived from thecoding sequence of SEQ ID NO:386 shown in FIG. 277.

FIG. 279 shows a nucleotide sequence (SEQ ID NO:388) of a nativesequence PRO1192 (UNQ606) cDNA, wherein SEQ ID NO:388 is a clonedesignated herein as “DNA62814-1521”.

FIG. 280 shows the amino acid sequence (SEQ ID NO:389) derived from thecoding sequence of SEQ ID NO:388 shown in FIG. 279.

FIG. 281 shows a nucleotide sequence (SEQ ID NO:393) of a nativesequence PRO1160 (UNQ590) cDNA, wherein SEQ ID NO:393 is a clonedesignated herein as “DNA62872-1509”.

FIG. 282 shows the amino acid sequence (SEQ ID NO:394) derived from thecoding sequence of SEQ ID NO:393 shown in FIG. 281.

FIG. 283 shows a nucleotide sequence (SEQ ID NO:398) of a nativesequence PRO1187 (UNQ601) cDNA, wherein SEQ ID NO:398 is a clonedesignated herein as “DNA62876-1517”.

FIG. 284 shows the amino acid sequence (SEQ ID NO:399) derived from thecoding sequence of SEQ ID NO:398 shown in FIG. 283.

FIG. 285 shows a nucleotide sequence (SEQ ID NO:400) of a nativesequence PRO1185 (UNQ599) cDNA, wherein SEQ ID NO:400 is a clonedesignated herein as “DNA62881-1515”.

FIG. 286 shows the amino acid sequence (SEQ ID NO:401) derived from thecoding sequence of SEQ ID NO:400 shown in FIG. 285.

FIG. 287 shows a nucleotide sequence (SEQ ID NO:402) of a nativesequence PRO1345 (UNQ700) cDNA, wherein SEQ ID NO:402 is a clonedesignated herein as “DNA64852-1589”.

FIG. 288 shows the amino acid sequence (SEQ ID NO:403) derived from thecoding sequence of SEQ ID NO:402 shown in FIG. 287.

FIG. 289 shows a nucleotide sequence (SEQ ID NO:407) of a nativesequence PRO1245 (UNQ629) cDNA, wherein SEQ ID NO:407 is a clonedesignated herein as “DNA64884-1527”.

FIG. 290 shows the amino acid sequence (SEQ ID NO:408) derived from thecoding sequence of SEQ ID NO:407 shown in FIG. 289.

FIG. 291 shows a nucleotide sequence (SEQ ID NO:409) of a nativesequence PRO1358 (UNQ707) cDNA, wherein SEQ ID NO:409 is a clonedesignated herein as “DNA64890-1612”.

FIG. 292 shows the amino acid sequence (SEQ ID NO:410) derived from thecoding sequence of SEQ ID NO:409 shown in FIG. 291.

FIG. 293 shows a nucleotide sequence (SEQ ID NO:411) of a nativesequence PRO1195 (UNQ608) cDNA, wherein SEQ ID NO:411 is a clonedesignated herein as “DNA65412-1523”.

FIG. 294 shows the amino acid sequence (SEQ ID NO:412) derived from thecoding sequence of SEQ ID NO:411 shown in FIG. 293.

FIG. 295 shows a nucleotide sequence (SEQ ID NO:413) of a nativesequence PRO1270 (UNQ640) cDNA, wherein SEQ ID NO:413 is a clonedesignated herein as “DNA66308-1537”.

FIG. 296 shows the amino acid sequence (SEQ ID NO:414) derived from thecoding sequence of SEQ ID NO:413 shown in FIG. 295.

FIG. 297 shows a nucleotide sequence (SEQ ID NO:415) of a nativesequence PRO1271 (UNQ641) cDNA, wherein SEQ ID NO:415 is a clonedesignated herein as “DNA66309-1538”.

FIG. 298 shows the amino acid sequence (SEQ ID NO:416) derived from thecoding sequence of SEQ ID NO:415 shown in FIG. 297.

FIG. 299 shows a nucleotide sequence (SEQ ID NO:417) of a nativesequence PRO1375 (UNQ712) cDNA, wherein SEQ ID NO:417 is a clonedesignated herein as “DNA67004-1614”.

FIG. 300 shows the amino acid sequence (SEQ ID NO:418) derived from thecoding sequence of SEQ ID NO:417 shown in FIG. 299.

FIG. 301 shows a nucleotide sequence (SEQ ID NO:419) of a nativesequence PRO1385 (UNQ720) cDNA, wherein SEQ ID NO:419 is a clonedesignated herein as “DNA68869-1610”.

FIG. 302 shows the amino acid sequence (SEQ ID NO:420) derived from thecoding sequence of SEQ ID NO:419 shown in FIG. 301.

FIG. 303 shows a nucleotide sequence (SEQ ID NO:421) of a nativesequence PRO1387 (UNQ722) cDNA, wherein SEQ ID NO:421 is a clonedesignated herein as “DNA68872-1620”.

FIG. 304 shows the amino acid sequence (SEQ ID NO:422) derived from thecoding sequence of SEQ ID NO:421 shown in FIG. 303.

FIG. 305 shows a nucleotide sequence (SEQ ID NO:423) of a nativesequence PRO1384 (UNQ721) cDNA, wherein SEQ ID NO:423 is a clonedesignated herein as “DNA71159-1617”.

FIG. 306 shows the amino acid sequence (SEQ ID NO:424) derived from thecoding sequence of SEQ ID NO:423 shown in FIG. 305.

FIG. 307 shows a nucleotide sequence (SEQ ID NO:494) of a nativesequence PRO183 cDNA, wherein SEQ ID NO:494 is a clone designated hereinas “DNA28498”.

FIG. 308 shows the amino acid sequence (SEQ ID NO:495) derived from thecoding sequence of SEQ ID NO:494 shown in FIG. 307.

FIG. 309 shows a nucleotide sequence (SEQ ID NO:496) of a nativesequence PRO184 cDNA, wherein SEQ ID NO:496 is a clone designated hereinas “DNA28500”.

FIG. 310 shows the amino acid sequence (SEQ ID NO:497) derived from thecoding sequence of SEQ ID NO:496 shown in FIG. 309.

FIG. 311 shows a nucleotide sequence (SEQ ID NO:498) of a nativesequence PRO185 cDNA, wherein SEQ ID NO:498 is a clone designated hereinas “DNA28503”.

FIG. 312 shows the amino acid sequence (SEQ ID NO:499) derived from thecoding sequence of SEQ ID NO:498 shown in FIG. 311.

FIG. 313 shows a nucleotide sequence (SEQ ID NO:500) of a nativesequence PRO331 cDNA, wherein SEQ ID NO:500 is a clone designated hereinas “DNA40981-1234”.

FIG. 314 shows the amino acid sequence (SEQ ID NO:501) derived from thecoding sequence of SEQ ID NO:500 shown in FIG. 313.

FIG. 315 shows a nucleotide sequence (SEQ ID NO:502) of a nativesequence PRO363 cDNA, wherein SEQ ID NO:502 is a clone designated hereinas “DNA45419-1252”.

FIG. 316 shows the amino acid sequence (SEQ ID NO:503) derived from thecoding sequence of SEQ ID NO:502 shown in FIG. 315.

FIG. 317 shows a nucleotide sequence (SEQ ID NO:504) of a nativesequence PRO5723 cDNA, wherein SEQ ID NO:504 is a clone designatedherein as “DNA82361”.

FIG. 318 shows the amino acid sequence (SEQ ID NO:505) derived from thecoding sequence of SEQ ID NO:504 shown in FIG. 317.

FIG. 319 shows a nucleotide sequence (SEQ ID NO:506) of a nativesequence PRO3301 cDNA, wherein SEQ ID NO:506 is a clone designatedherein as “DNA88002”.

FIG. 320 shows the amino acid sequence (SEQ ID NO:507) derived from thecoding sequence of SEQ ID NO:506 shown in FIG. 319.

FIG. 321 shows a nucleotide sequence (SEQ ID NO:508) of a nativesequence PRO9940 cDNA, wherein SEQ ID NO:508 is a clone designatedherein as “DNA92282”.

FIG. 322 shows the amino acid sequence (SEQ ID NO:509) derived from thecoding sequence of SEQ ID NO:508 shown in FIG. 321.

FIG. 323 shows a nucleotide sequence (SEQ ID NO:510) of a nativesequence PRO9828 cDNA, wherein SEQ ID NO:510 is a clone designatedherein as “DNA142238-2768”.

FIG. 324 shows the amino acid sequence (SEQ ID NO:511) derived from thecoding sequence of SEQ ID NO:510 shown in FIG. 323.

FIG. 325 shows a nucleotide sequence (SEQ ID NO:512) of a nativesequence PRO7170 cDNA, wherein SEQ ID NO:512 is a clone designatedherein as “DNA108722-2743”.

FIG. 326 shows the amino acid sequence (SEQ ID NO:513) derived from thecoding sequence of SEQ ID NO:512 shown in FIG. 325.

FIG. 327 shows a nucleotide sequence (SEQ ID NO:514) of a nativesequence PRO361 cDNA, wherein SEQ ID NO:514 is a clone designated hereinas “DNA45410-1250”.

FIG. 328 shows the amino acid sequence (SEQ ID NO:515) derived from thecoding sequence of SEQ ID NO:514 shown in FIG. 327.

FIG. 329 shows a nucleotide sequence (SEQ ID NO:516) of a nativesequence PRO846 cDNA, wherein SEQ ID NO:516 is a clone designated hereinas “DNA44196-1353”.

FIG. 330 shows the amino acid sequence (SEQ ID NO:517) derived from thecoding sequence of SEQ ID NO:516 shown in FIG. 329.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

I. Definitions

The terms “PRO polypeptide” and “PRO” as used herein and whenimmediately followed by a numerical designation refer to variouspolypeptides, wherein the complete designation (i.e., PRO/number) refersto specific polypeptide sequences as described herein. The terms“PRO/number polypeptide” and “PRO/number” wherein the term “number” isprovided as an actual numerical designation as used herein encompassnative sequence polypeptides and polypeptide variants (which are furtherdefined herein). The PRO polypeptides described herein may be isolatedfrom a variety of sources, such as from human tissue types or fromanother source, or prepared by recombinant or synthetic methods.

A “native sequence PRO polypeptide” comprises a polypeptide having thesame amino acid sequence as the corresponding PRO polypeptide derivedfrom nature. Such native sequence PRO polypeptides can be isolated fromnature or can be produced by recombinant or synthetic means. The term“native sequence PRO polypeptide” specifically encompassesnaturally-occurring truncated or secreted forms of the specific PROpolypeptide (e.g., an extracellular domain sequence),naturally-occurring variant forms (e.g., alternatively spliced forms)and naturally-occurring allelic variants of the polypeptide. In variousembodiments of the invention, the native sequence PRO polypeptidesdisclosed herein are mature or full-length native sequence polypeptidescomprising the full-length amino acids sequences shown in theaccompanying figures. Start and stop codons are shown in bold font andunderlined in the figures. However, while the PRO polypeptide disclosedin the accompanying figures are shown to begin with methionine residuesdesignated herein as amino acid position 1 in the figures, it isconceivable and possible that other methionine residues located eitherupstream or downstream from the amino acid position 1 in the figures maybe employed as the starting amino acid residue for the PRO polypeptides.

The PRO polypeptide “extracellular domain” or “ECD” refers to a form ofthe PRO polypeptide which is essentially free of the transmembrane andcytoplasmic domains. Ordinarily, a PRO polypeptide ECD will have lessthan 1% of such transmembrane and/or cytoplasmic domains and preferably,will have less than 0.5% of such domains. It will be understood that anytransmembrane domains identified for the PRO polypeptides of the presentinvention are identified pursuant to criteria routinely employed in theart for identifying that type of hydrophobic domain. The exactboundaries of a transmembrane domain may vary but most likely by no morethan about 5 amino acids at either end of the domain as initiallyidentified herein. Optionally, therefore, an extracellular domain of aPRO polypeptide may contain from about 5 or fewer amino acids on eitherside of the transmembrane domain/extracellular domain boundary asidentified in the Examples or specification and such polypeptides, withor without the associated signal peptide, and nucleic acid encodingthem, are contemplated by the present invention.

The approximate location of the “signal peptides” of the various PROpolypeptides disclosed herein are shown in the present specificationand/or the accompanying figures. It is noted, however, that theC-terminal boundary of a signal peptide may vary, but most likely by nomore than about 5 amino acids on either side of the signal peptideC-terminal boundary as initially identified herein, wherein theC-terminal boundary of the signal peptide may be identified pursuant tocriteria routinely employed in the art for identifying that type ofamino acid sequence element (e.g., Nielsen et al., Prot. Eng. 10:1–6(1997) and von Heinje et al., Nucl. Acids. Res. 14:4683–4690 (1986)).Moreover, it is also recognized that, in some cases, cleavage of asignal sequence from a secreted polypeptide is not entirely uniform,resulting in more than one secreted species. These mature polypeptides,where the signal peptide is cleaved within no more than about 5 aminoacids on either side of the C-terminal boundary of the signal peptide asidentified herein, and the polynucleotides encoding them, arecontemplated by the present invention.

“PRO polypeptide variant” means an active PRO polypeptide as definedabove or below having at least about 80% amino acid sequence identitywith a full-length native sequence PRO polypeptide sequence as disclosedherein, a PRO polypeptide sequence lacking the signal peptide asdisclosed herein, an extracellular domain of a PRO polypeptide, with orwithout the signal peptide, as disclosed herein or any other fragment ofa full-length PRO polypeptide sequence as disclosed herein. Such PROpolypeptide variants include, for instance, PRO polypeptides wherein oneor more amino acid residues are added, or deleted, at the N- orC-terminus of the full-length native amino acid sequence. Ordinarily, aPRO polypeptide variant will have at least about 80% amino acid sequenceidentity, preferably at least about 81% amino acid sequence identity,more preferably at least about 82% amino acid sequence identity, morepreferably at least about 83% amino acid sequence identity, morepreferably at least about 84% amino acid sequence identity, morepreferably at least about 85% amino acid sequence identity, morepreferably at least about 86% amino acid sequence identity, morepreferably at least about 87% amino acid sequence identity, morepreferably at least about 88% amino acid sequence identity, morepreferably at least about 89% amino acid sequence identity, morepreferably at least about 90% amino acid sequence identity, morepreferably at least about 91% amino acid sequence identity, morepreferably at least about 92% amino acid sequence identity, morepreferably at least about 93% amino acid sequence identity, morepreferably at least about 94% amino acid sequence identity, morepreferably at least about 95% amino acid sequence identity, morepreferably at least about 96% amino acid sequence identity, morepreferably at least about 97% amino acid sequence identity, morepreferably at least about 98% amino acid sequence identity and mostpreferably at least about 99% amino acid sequence identity with afull-length native sequence PRO polypeptide sequence as disclosedherein, a PRO polypeptide sequence lacking the signal peptide asdisclosed herein, an extracellular domain of a PRO polypeptide, with orwithout the signal peptide, as disclosed herein or any otherspecifically defined fragment of a full-length PRO polypeptide sequenceas disclosed herein. Ordinarily, PRO variant polypeptides are at leastabout 10 amino acids in length, often at least about 20 amino acids inlength, more often at least about 30 amino acids in length, more oftenat least about 40 amino acids in length, more often at least about 50amino acids in length, more often at least about 60 amino acids inlength, more often at least about 70 amino acids in length, more oftenat least about 80 amino acids in length, more often at least about 90amino acids in length, more often at least about 100 amino acids inlength, more often at least about 150 amino acids in length, more oftenat least about 200 amino acids in length, more often at least about 300amino acids in length, or more.

“Percent (%) amino acid sequence identity” with respect to the PROpolypeptide sequences identified herein is defined as the percentage ofamino acid residues in a candidate sequence that are identical with theamino acid residues in the specific PRO polypeptide sequence, afteraligning the sequences and introducing gaps, if necessary, to achievethe maximum percent sequence identity, and not considering anyconservative substitutions as part of the sequence identity. Alignmentfor purposes of determining percent amino acid sequence identity can beachieved in various ways that are within the skill in the art, forinstance, using publicly available computer software such as BLAST,BLAST-2, ALIGN or Megalign (DNASTAR) software. Those skilled in the artcan determine appropriate parameters for measuring alignment, includingany algorithms needed to achieve maximal alignment over the full lengthof the sequences being compared. For purposes herein, however, % aminoacid sequence identity values are generated using the sequencecomparison computer program ALIGN-2, wherein the complete source codefor the ALIGN-2 program is provided in Table 1 below. The ALIGN-2sequence comparison computer program was authored by Genentech, Inc. andthe source code shown in Table 1 below has been filed with userdocumentation in the U.S. Copyright Office, Washington D.C., 20559,where it is registered under U.S. Copyright Registration No. TXU510087.The ALIGN-2 program is publicly available through Genentech, Inc., SouthSan Francisco, Calif. or may be compiled from the source code providedin Table 1 below. The ALIGN-2 program should be compiled for use on aUNIX operating system, preferably digital UNIX V4.0D. All sequencecomparison parameters are set by the ALIGN-2 program and do not vary.

In situations where ALIGN-2 is employed for amino acid sequencecomparisons, the % amino acid sequence identity of a given amino acidsequence A to, with, or against a given amino acid sequence B (which canalternatively be phrased as a given amino acid sequence A that has orcomprises a certain % amino acid sequence identity to, with, or againsta given amino acid sequence B) is calculated as follows:100 times the fraction X/Ywhere X is the number of amino acid residues scored as identical matchesby the sequence alignment program ALIGN-2 in that program's alignment ofA and B, and where Y is the total number of amino acid residues in B. Itwill be appreciated that where the length of amino acid sequence A isnot equal to the length of amino acid sequence B, the % amino acidsequence identity of A to B will not equal the % amino acid sequenceidentity of B to A. As examples of % amino acid sequence identitycalculations using this method, Tables 2 and 3 demonstrate how tocalculate the % amino acid sequence identity of the amino acid sequencedesignated “Comparison Protein” to the amino acid sequence designated“PRO”, wherein “PRO” represents the amino acid sequence of ahypothetical PRO polypeptide of interest, “Comparison Protein”represents the amino acid sequence of a polypeptide against which the“PRO” polypeptide of interest is being compared, and “X, “Y” and “Z”each represent different hypothetical amino acid residues.

Unless specifically stated otherwise, all % amino acid sequence identityvalues used herein are obtained as described in the immediatelypreceding paragraph using the ALIGN-2 computer program. However, % aminoacid sequence identity values may also be obtained as described below byusing the WU-BLAST-2 computer program (Altschul et al., Methods inEnzymology 266:460–480 (1996)). Most of the WU-BLAST-2 search parametersare set to the default values. Those not set to default values, i.e.,the adjustable parameters, are set with the following values: overlapspan=1, overlap fraction=0.125, word threshold (T)=11, and scoringmatrix=BLOSUM62. When WU-BLAST-2 is employed, a % amino acid sequenceidentity value is determined by dividing (a) the number of matchingidentical amino acid residues between the amino acid sequence of the PROpolypeptide of interest having a sequence derived from the native PROpolypeptide and the comparison amino acid sequence of interest (i.e.,the sequence against which the PRO polypeptide of interest is beingcompared which may be a PRO variant polypeptide) as determined byWU-BLAST-2 by (b) the total number of amino acid residues of the PROpolypeptide of interest. For example, in the statement “a polypeptidecomprising an the amino acid sequence A which has or having at least 80%amino acid sequence identity to the amino acid sequence B”, the aminoacid sequence A is the comparison amino acid sequence of interest andthe amino acid sequence B is the amino acid sequence of the PROpolypeptide of interest.

Percent amino acid sequence identity may also be determined using thesequence comparison program NCBI-BLAST2 (Altschul et al., Nucleic AcidsRes. 25:3389–3402 (1997)). NCBI-BLAST2 uses several search parameters,wherein all of those search parameters are set to default valuesincluding, for example, unmask=yes, strand=all, expected occurrences=10,minimum low complexity length=15/5, multi-pass e-value=0.01, constantfor multi-pass=25, dropoff for final gapped alignment=25 and scoringmatrix=BLOSUM62.

In situations where NCBI-BLAST2 is employed for amino acid sequencecomparisons, the % amino acid sequence identity of a given amino acidsequence A to, with, or against a given amino acid sequence B (which canalternatively be phrased as a given amino acid sequence A that has orcomprises a certain % amino acid sequence identity to, with, or againsta given amino acid sequence B) is calculated as follows:100 times the fraction X/Ywhere X is the number of amino acid residues scored as identical matchesby the sequence alignment program NCBI-BLAST2 in that program'salignment of A and B, and where Y is the total number of amino acidresidues in B. It will be appreciated that where the length of aminoacid sequence A is not equal to the length of amino acid sequence B, the% amino acid sequence identity of A to B will not equal the % amino acidsequence identity of B to A.

“PRO variant polynucleotide” or “PRO variant nucleic acid sequence”means a nucleic acid molecule which encodes an active PRO polypeptide asdefined below and which has at least about 80% nucleic acid sequenceidentity with a nucleotide acid sequence encoding a full-length nativesequence PRO polypeptide sequence as disclosed herein, a full-lengthnative sequence PRO polypeptide sequence lacking the signal peptide asdisclosed herein, an extracellular domain of a PRO polypeptide, with orwithout the signal peptide, as disclosed herein or any other fragment ofa full-length PRO polypeptide sequence as disclosed herein. Ordinarily,a PRO variant polynucleotide will have at least about 80% nucleic acidsequence identity, more preferably at least about 81% nucleic acidsequence identity, more preferably at least about 82% nucleic acidsequence identity, more preferably at least about 83% nucleic acidsequence identity, more preferably at least about 84% nucleic acidsequence identity, more preferably at least about 85% nucleic acidsequence identity, more preferably at least about 86% nucleic acidsequence identity, more preferably at least about 87% nucleic acidsequence identity, more preferably at least about 88% nucleic acidsequence identity, more preferably at least about 89% nucleic acidsequence identity, more preferably at least about 90% nucleic acidsequence identity, more preferably at least about 91% nucleic acidsequence identity, more preferably at least about 92% nucleic acidsequence identity, more preferably at least about 93% nucleic acidsequence identity, more preferably at least about 94% nucleic acidsequence identity, more preferably at least about 95% nucleic acidsequence identity, more preferably at least about 96% nucleic acidsequence identity, more preferably at least about 97% nucleic acidsequence identity, more preferably at least about 98% nucleic acidsequence identity and yet more preferably at least about 99% nucleicacid sequence identity with a nucleic acid sequence encoding afull-length native sequence PRO polypeptide sequence as disclosedherein, a full-length native sequence PRO polypeptide sequence lackingthe signal peptide as disclosed herein, an extracellular domain of a PROpolypeptide, with or without the signal sequence, as disclosed herein orany other fragment of a full-length PRO polypeptide sequence asdisclosed herein. Variants do not encompass the native nucleotidesequence.

Ordinarily, PRO variant polynucleotides are at least about 30nucleotides in length, often at least about 60 nucleotides in length,more often at least about 90 nucleotides in length, more often at leastabout 120 nucleotides in length, more often at least about 150nucleotides in length, more often at least about 180 nucleotides inlength, more often at least about 210 nucleotides in length, more oftenat least about 240 nucleotides in length, more often at least about 270nucleotides in length, more often at least about 300 nucleotides inlength, more often at least about 450 nucleotides in length, more oftenat least about 600 nucleotides in length, more often at least about 900nucleotides in length, or more.

“Percent (%) nucleic acid sequence identity” with respect toPRO-encoding nucleic acid sequences identified herein is defined as thepercentage of nucleotides in a candidate sequence that are identicalwith the nucleotides in the PRO nucleic acid sequence of interest, afteraligning the sequences and introducing gaps, if necessary, to achievethe maximum percent sequence identity. Alignment for purposes ofdetermining percent nucleic acid sequence identity can be achieved invarious ways that are within the skill in the art, for instance, usingpublicly available computer software such as BLAST, BLAST-2, ALIGN orMegalign (DNASTAR) software. For purposes herein, however, % nucleicacid sequence identity values are generated using the sequencecomparison computer program ALIGN-2, wherein the complete source codefor the ALIGN-2 program is provided in Table 1 below. The ALIGN-2sequence comparison computer program was authored by Genentech, Inc. andthe source code shown in Table 1 below has been filed with userdocumentation in the U.S. Copyright Office, Washington D.C., 20559,where it is registered under U.S. Copyright Registration No. TXU510087.The ALIGN-2 program is publicly available through Genentech, Inc., SouthSan Francisco, Calif. or may be compiled from the source code providedin Table 1 below.

The ALIGN-2 program should be compiled for use on a UNIX operatingsystem, preferably digital UNIX V4.0D. All sequence comparisonparameters are set by the ALIGN-2 program and do not vary.

In situations where ALIGN-2 is employed for nucleic acid sequencecomparisons, the % nucleic acid sequence identity of a given nucleicacid sequence C to, with, or against a given nucleic acid sequence D(which can alternatively be phrased as a given nucleic acid sequence Cthat has or comprises a certain % nucleic acid sequence identity to,with, or against a given nucleic acid sequence D) is calculated asfollows:100 times the fraction W/Zwhere W is the number of nucleotides scored as identical matches by thesequence alignment program ALIGN-2 in that program's alignment of C andD, and where Z is the total number of nucleotides in D. It will beappreciated that where the length of nucleic acid sequence C is notequal to the length of nucleic acid sequence D, the % nucleic acidsequence identity of C to D will not equal the % nucleic acid sequenceidentity of D to C. As examples of % nucleic acid sequence identitycalculations, Tables 4 and 5, demonstrate how to calculate the % nucleicacid sequence identity of the nucleic acid sequence designated“Comparison DNA” to the nucleic acid sequence designated “PRO-DNA”,wherein “PRO-DNA” represents a hypothetical PRO-encoding nucleic acidsequence of interest, “Comparison DNA” represents the nucleotidesequence of a nucleic acid molecule against which the “PRO-DNA” nucleicacid molecule of interest is being compared, and “N”, “L” and “V” eachrepresent different hypothetical nucleotides.

Unless specifically stated otherwise, all % nucleic acid sequenceidentity values used herein are obtained as described in the immediatelypreceding paragraph using the ALIGN-2 computer program. However, %nucleic acid sequence identity values may also be obtained as describedbelow by using the WU-BLAST-2 computer program (Altschul et al., Methodsin Enzymology 266:460–480(1996)). Most of the WU-BLAST-2 searchparameters are set to the default values. Those not set to defaultvalues, i.e., the adjustable parameters, are set with the followingvalues: overlap span=1, overlap fraction=0.125, word threshold (T)=11,and scoring matrix=BLOSUM62. When WU-BLAST-2 is employed, a % nucleicacid sequence identity value is determined by dividing (a) the number ofmatching identical nucleotides between the nucleic acid sequence of thePRO polypeptide-encoding nucleic acid molecule of interest having asequence derived from the native sequence PRO polypeptide-encodingnucleic acid and the comparison nucleic acid molecule of interest (i.e.,the sequence against which the PRO polypeptide-encoding nucleic acidmolecule of interest is being compared which may be a variant PROpolynucleotide) as determined by WU-BLAST-2 by (b) the total number ofnucleotides of the PRO polypeptide-encoding nucleic acid molecule ofinterest. For example, in the statement “an isolated nucleic acidmolecule comprising a nucleic acid sequence A which has or having atleast 80% nucleic acid sequence identity to the nucleic acid sequenceB”, the nucleic acid sequence A is the comparison nucleic acid moleculeof interest and the nucleic acid sequence B is the nucleic acid sequenceof the PRO polypeptide-encoding nucleic acid molecule of interest.

Percent nucleic acid sequence identity may also be determined using thesequence comparison program NCBI-BLAST2 (Altschul et al., Nucleic AcidsRes. 25:3389–3402 (1997)). NCBI-BLAST2 uses several search parameters,wherein all of those search parameters are set to default valuesincluding, for example, unmask=yes, strand=all, expected occurrences=10,minimum low complexity length=15/5, multi-pass e-value=0.01, constantfor multi-pass=25, dropoff for final gapped alignment=25 and scoringmatrix=BLOSUM62.

In situations where NCBI-BLAST2 is employed for sequence comparisons,the % nucleic acid sequence identity of a given nucleic acid sequence Cto, with, or against a given nucleic acid sequence D (which canalternatively be phrased as a given nucleic acid sequence C that has orcomprises a certain % nucleic acid sequence identity to, with, oragainst a given nucleic acid sequence D) is calculated as follows:100 times the fraction W/Zwhere W is the number of nucleotides scored as identical matches by thesequence alignment program NCBI-BLAST2 in that program's alignment of Cand D, and where Z is the total number of nucleotides in D. It will beappreciated that where the length of nucleic acid sequence C is notequal to the length of nucleic acid sequence D, the % nucleic acidsequence identity of C to D will not equal the % nucleic acid sequenceidentity of D to C.

In other embodiments, PRO variant polynucleotides are nucleic acidmolecules that encode an active PRO polypeptide and which are capable ofhybridizing, preferably under stringent hybridization and washconditions, to nucleotide sequences encoding a full-length PROpolypeptide as disclosed herein. PRO variant polypeptides may be thosethat are encoded by a PRO variant polynucleotide.

The term “positives”, in the context of sequence comparison performed asdescribed above, includes residues in the sequences compared that arenot identical but have similar properties (e.g. as a result ofconservative substitutions, see Table 6 below). For purposes herein, the% value of positives is determined by dividing (a) the number of aminoacid residues scoring a positive value between the PRO polypeptide aminoacid sequence of interest having a sequence derived from the native PROpolypeptide sequence and the comparison amino acid sequence of interest(i.e., the amino acid sequence against which the PRO polypeptidesequence is being compared) as determined in the BLOSUM62 matrix ofWU-BLAST-2 by (b) the total number of amino acid residues of the PROpolypeptide of interest.

Unless specifically stated otherwise, the % value of positives iscalculated as described in the immediately preceding paragraph. However,in the context of the amino acid sequence identity comparisons performedas described for ALIGN-2 and NCBI-BLAST-2 above, includes amino acidresidues in the sequences compared that are not only identical, but alsothose that have similar properties. Amino acid residues that score apositive value to an amino acid residue of interest are those that areeither identical to the amino acid residue of interest or are apreferred substitution (as defined in Table 6 below) of the amino acidresidue of interest.

For amino acid sequence comparisons using ALIGN-2 or NCBI-BLAST2, the %value of positives of a given amino acid sequence A to, with, or againsta given amino acid sequence B (which can alternatively be phrased as agiven amino acid sequence A that has or comprises a certain % positivesto, with, or against a given amino acid sequence B) is calculated asfollows:100 times the fraction X/Ywhere X is the number of amino acid residues scoring a positive value asdefined above by the sequence alignment program ALIGN-2 or NCBI-BLAST2in that program's alignment of A and B, and where Y is the total numberof amino acid residues in B. It will be appreciated that where thelength of amino acid sequence A is not equal to the length of amino acidsequence B, the % positives of A to B will not equal the % positives ofB to A.

“Isolated,” when used to describe the various polypeptides disclosedherein, means polypeptide that has been identified and separated and/orrecovered from a component of its natural environment. Contaminantcomponents of its natural environment are materials that would typicallyinterfere with diagnostic or therapeutic uses for the polypeptide, andmay include enzymes, hormones, and other proteinaceous ornon-proteinaceous solutes. In preferred embodiments, the polypeptidewill be purified (1) to a degree sufficient to obtain at least 15residues of N-terminal or internal amino acid sequence by use of aspinning cup sequenator, or (2) to homogeneity by SDS-PAGE undernon-reducing or reducing conditions using Coomassie blue or, preferably,silver stain. Isolated polypeptide includes polypeptide in situ withinrecombinant cells, since at least one component of the PRO polypeptidenatural environment will not be present. Ordinarily, however, isolatedpolypeptide will be prepared by at least one purification step.

An “isolated” PRO polypeptide-encoding nucleic acid or otherpolypeptide-encoding nucleic acid is a nucleic acid molecule that isidentified and separated from at least one contaminant nucleic acidmolecule with which it is ordinarily associated in the natural source ofthe polypeptide-encoding nucleic acid. An isolated polypeptide-encodingnucleic acid molecule is other than in the form or setting in which itis found in nature. Isolated polypeptide-encoding nucleic acid moleculestherefore are distinguished from the specific polypeptide-encodingnucleic acid molecule as it exists in natural cells. However, anisolated polypeptide-encoding nucleic acid molecule includespolypeptide-encoding nucleic acid molecules contained in cells thatordinarily express the polypeptide where, for example, the nucleic acidmolecule is in a chromosomal location different from that of naturalcells.

The term “control sequences” refers to DNA sequences necessary for theexpression of an operably linked coding sequence in a particular hostorganism. The control sequences that are suitable for prokaryotes, forexample, include a promoter, optionally an operator sequence, and aribosome binding site. Eukaryotic cells are known to utilize promoters,polyadenylation signals, and enhancers.

Nucleic acid is “operably linked” when it is placed into a functionalrelationship with another nucleic acid sequence. For example, DNA for apresequence or secretory leader is operably linked to DNA for apolypeptide if it is expressed as a preprotein that participates in thesecretion of the polypeptide; a promoter or enhancer is operably linkedto a coding sequence if it affects the transcription of the sequence; ora ribosome binding site is operably linked to a coding sequence if it ispositioned so as to facilitate translation. Generally, “operably linked”means that the DNA sequences being linked are contiguous, and, in thecase of a secretory leader, contiguous and in reading phase. However,enhancers do not have to be contiguous. Linking is accomplished byligation at convenient restriction sites. If such sites do not exist,the synthetic oligonucleotide adaptors or linkers are used in accordancewith conventional practice.

The term “antibody” is used in the broadest sense and specificallycovers, for example, single anti-PRO monoclonal antibodies (includingagonist, antagonist, and neutralizing antibodies), anti-PRO antibodycompositions with polyepitopic specificity, single chain anti-PROantibodies, and fragments of anti-PRO antibodies (see below). The term“monoclonal antibody” as used herein refers to an antibody obtained froma population of substantially homogeneous antibodies, i.e., theindividual antibodies comprising the population are identical except forpossible naturally-occurring mutations that may be present in minoramounts.

“Stringency” of hybridization reactions is readily determinable by oneof ordinary skill in the art, and generally is an empirical calculationdependent upon probe length, washing temperature, and saltconcentration. In general, longer probes require higher temperatures forproper annealing, while shorter probes need lower temperatures.Hybridization generally depends on the ability of denatured DNA toreanneal when complementary strands are present in an environment belowtheir melting temperature. The higher the degree of desired homologybetween the probe and hybridizable sequence, the higher the relativetemperature which can be used. As a result, it follows that higherrelative temperatures would tend to make the reaction conditions morestringent, while lower temperatures less so. For additional details andexplanation of stringency of hybridization reactions, see Ausubel etal., Current Protocols in Molecular Biology, Wiley IntersciencePublishers, (1995).

“Stringent conditions” or “high stringency conditions”, as definedherein, may be identified by those that: (1) employ low ionic strengthand high temperature for washing, for example 0.015 M sodiumchloride/0.0015 M sodium citrate/0.1% sodium dodecyl sulfate at 50° C.;(2) employ during hybridization a denaturing agent, such as formamide,for example, 50% (v/v) formamide with 0.1% bovine serum albumin/0.1%Ficoll/0.1% polyvinylpyrrolidone/50 mM sodium phosphate buffer at pH 6.5with 750 mM sodium chloride, 75 mM sodium citrate at 42° C.; or (3)employ 50% formamide, 5×SSC (0.75 M NaCl, 0.075 M sodium citrate), 50 mMsodium phosphate (pH 6.8), 0.1% sodium pyrophosphate, 5× Denhardt'ssolution, sonicated salmon sperm DNA (50 μg/ml), 0.1% SDS, and 10%dextran sulfate at 42° C., with washes at 42° C. in 0.2×SSC (sodiumchloride/sodium citrate) and 50% formamide at 55° C., followed by ahigh-stringency wash consisting of 0.1×SSC containing EDTA at 55° C.

“Moderately stringent conditions” may be identified as described bySambrook et al., Molecular Cloning: A Laboratory Manual, New York: ColdSpring Harbor Press, 1989, and include the use of washing solution andhybridization conditions (e.g., temperature, ionic strength and % SDS)less stringent that those described above. An example of moderatelystringent conditions is overnight incubation at 37° C. in a solutioncomprising: 20% formamide, 5×SSC (150 mM NaCl, 15 mM trisodium citrate),50 mM sodium phosphate (pH 7.6), 5× Denhardt's solution, 10% dextransulfate, and 20 mg/ml denatured sheared salmon sperm DNA, followed bywashing the filters in 1×SSC at about 37–50° C. The skilled artisan willrecognize how to adjust the temperature, ionic strength, etc. asnecessary to accommodate factors such as probe length and the like.

The term “epitope tagged” when used herein refers to a chimericpolypeptide comprising a PRO polypeptide fused to a “tag polypeptide”.The tag polypeptide has enough residues to provide an epitope againstwhich an antibody can be made, yet is short enough such that it does notinterfere with activity of the polypeptide to which it is fused. The tagpolypeptide preferably also is fairly unique so that the antibody doesnot substantially cross-react with other epitopes. Suitable tagpolypeptides generally have at least six amino acid residues and usuallybetween about 8 and 50 amino acid residues (preferably, between about 10and 20 amino acid residues).

As used herein, the term “immunoadhesin” designates antibody-likemolecules which combine the binding specificity of a heterologousprotein (an “adhesin”) with the effector functions of immunoglobulinconstant domains. Structurally, the immunoadhesins comprise a fusion ofan amino acid sequence with the desired binding specificity which isother than the antigen recognition and binding site of an antibody(i.e., is “heterologous”), and an immunoglobulin constant domainsequence. The adhesin part of an immunoadhesin molecule typically is acontiguous amino acid sequence comprising at least the binding site of areceptor or a ligand. The immunoglobulin constant domain sequence in theimmunoadhesin may be obtained from any immunoglobulin, such as IgG-1,IgG-2, IgG-3, or IgG-4 subtypes, IgA (including IgA-1 and IgA-2), IgE,IgD or IgM.

“Active” or “activity” for the purposes herein refers to form(s) of aPRO polypeptide which retain a biological and/or an immunologicalactivity of native or naturally-occurring PRO, wherein “biological”activity refers to a biological function (either inhibitory orstimulatory) caused by a native or naturally-occurring PRO other thanthe ability to induce the production of an antibody against an antigenicepitope possessed by a native or naturally-occurring PRO and an“immunological” activity refers to the ability to induce the productionof an antibody against an antigenic epitope possessed by a native ornaturally-occurring PRO.

The term “antagonist” is used in the broadest sense, and includes anymolecule that partially or fully blocks, inhibits, or neutralizes abiological activity of a native PRO polypeptide disclosed herein. In asimilar manner, the term “agonist” is used in the broadest sense andincludes any molecule that mimics a biological activity of a native PROpolypeptide disclosed herein. Suitable agonist or antagonist moleculesspecifically include agonist or antagonist antibodies or antibodyfragments, fragments or amino acid sequence variants of native PROpolypeptides, peptides, antisense oligonucleotides, small organicmolecules, etc. Methods for identifying agonists or antagonists of a PROpolypeptide may comprise contacting a PRO polypeptide with a candidateagonist or antagonist molecule and measuring a detectable change in oneor more biological activities normally associated with the PROpolypeptide.

“Treatment” refers to both therapeutic treatment and prophylactic orpreventative measures, wherein the object is to prevent or slow down(lessen) the targeted pathologic condition or disorder. Those in need oftreatment include those already with the disorder as well as those proneto have the disorder or those in whom the disorder is to be prevented.

“Chronic” administration refers to administration of the agent(s) in acontinuous mode as opposed to an acute mode, so as to maintain theinitial therapeutic effect (activity) for an extended period of time.

“Intermittent” administration is treatment that is not consecutivelydone without interruption, but rather is cyclic in nature.

“Mammal” for purposes of treatment refers to any animal classified as amammal, including humans, domestic and farm animals, and zoo, sports, orpet animals, such as dogs, cats, cattle, horses, sheep, pigs, goats,rabbits, etc. Preferably, the mammal is human.

Administration “in combination with” one or more further therapeuticagents includes simultaneous (concurrent) and consecutive administrationin any order.

“Carriers” as used herein include pharmaceutically acceptable carriers,excipients, or stabilizers which are nontoxic to the cell or mammalbeing exposed thereto at the dosages and concentrations employed. Oftenthe physiologically acceptable carrier is an aqueous pH bufferedsolution. Examples of physiologically acceptable carriers includebuffers such as phosphate, citrate, and other organic acids;antioxidants including ascorbic acid; low molecular weight (less thanabout 10 residues) polypeptide; proteins, such as serum albumin,gelatin, or immunoglobulins; hydrophilic polymers such aspolyvinylpyrrolidone; amino acids such as glycine, glutamine,asparagine, arginine or lysine; monosaccharides, disaccharides, andother carbohydrates including glucose, mannose, or dextrins; chelatingagents such as EDTA; sugar alcohols such as mannitol or sorbitol;salt-forming counterions such as sodium; and/or nonionic surfactantssuch as TWEEN™, polyethylene glycol (PEG), and PLURONICS™.

“Antibody fragments” comprise a portion of an intact antibody,preferably the antigen binding or variable region of the intactantibody. Examples of antibody fragments include Fab, Fab′, F(ab′)₂, andFv fragments; diabodies; linear antibodies (Zapata et al., Protein Eng.8(10): 1057–1062 [1995]); single-chain antibody molecules; andmultispecific antibodies formed from antibody fragments.

Papain digestion of antibodies produces two identical antigen-bindingfragments, called “Fab” fragments, each with a single antigen-bindingsite, and a residual “Fc” fragment, a designation reflecting the abilityto crystallize readily. Pepsin treatment yields an F(ab′)₂ fragment thathas two antigen-combining sites and is still capable of cross-linkingantigen.

“Fv” is the minimum antibody fragment which contains a completeantigen-recognition and -binding site. This region consists of a dimerof one heavy- and one light-chain variable domain in tight, non-covalentassociation. It is in this configuration that the three CDRs of eachvariable domain interact to define an antigen-binding site on thesurface of the V_(H)–V_(L) dimer. Collectively, the six CDRs conferantigen-binding specificity to the antibody. However, even a singlevariable domain (or half of an Fv comprising only three CDRs specificfor an antigen) has the ability to recognize and bind antigen, althoughat a lower affinity than the entire binding site.

The Fab fragment also contains the constant domain of the light chainand the first constant domain (CH1) of the heavy chain. Fab fragmentsdiffer from Fab′ fragments by the addition of a few residues at thecarboxy terminus of the heavy chain CH1 domain including one or morecysteines from the antibody hinge region. Fab′-SH is the designationherein for Fab′ in which the cysteine residue(s) of the constant domainsbear a free thiol group. F(ab′)₂ antibody fragments originally wereproduced as pairs of Fab′ fragments which have hinge cysteines betweenthem. Other chemical couplings of antibody fragments are also known.

The “light chains” of antibodies (immunoglobulins) from any vertebratespecies can be assigned to one of two clearly distinct types, calledkappa and lambda, based on the amino acid sequences of their constantdomains.

Depending on the amino acid sequence of the constant domain of theirheavy chains, immunoglobulins can be assigned to different classes.There are five major classes of immunoglobulins: IgA, IgD, IgE, IgG, andIgM, and several of these may be further divided into subclasses(isotypes), e.g., IgG1, IgG2, IgG3, IgG4, IgA, and IgA2.

“Single-chain Fv” or “sFv” antibody fragments comprise the V_(H) andV_(L) domains of antibody, wherein these domains are present in a singlepolypeptide chain. Preferably, the Fv polypeptide further comprises apolypeptide linker between the V_(H) and V_(L) domains which enables thesFv to form the desired structure for antigen binding. For a review ofsFv, see Pluckthun in The Pharmacology of Monoclonal Antibodies, vol.113, Rosenburg and Moore eds., Springer-Verlag, New York, pp. 269–315(1994).

The term “diabodies” refers to small antibody fragments with twoantigen-binding sites, which fragments comprise a heavy-chain variabledomain (V_(H)) connected to a light-chain variable domain (VL) in thesame polypeptide chain (V_(H)-V_(L)). By using a linker that is tooshort to allow pairing between the two domains on the same chain, thedomains are forced to pair with the complementary domains of anotherchain and create two antigen-binding sites. Diabodies are described morefully in, for example, EP 404,097; WO 93/11161; and Hollinger et al.,Proc. Natl. Acad. Sci. USA, 90:6444–6448 (1993).

An “isolated” antibody is one which has been identified and separatedand/or recovered from a component of its natural environment.Contaminant components of its natural environment are materials whichwould interfere with diagnostic or therapeutic uses for the antibody,and may include enzymes, hormones, and other proteinaceous ornonproteinaceous solutes. In preferred embodiments, the antibody will bepurified (1) to greater than 95% by weight of antibody as determined bythe Lowry method, and most preferably more than 99% by weight, (2) to adegree sufficient to obtain at least 15 residues of N-terminal orinternal amino acid sequence by use of a spinning cup sequenator, or (3)to homogeneity by SDS-PAGE under reducing or nonreducing conditionsusing Coomassie blue or, preferably, silver stain. Isolated antibodyincludes the antibody in situ within recombinant cells since at leastone component of the antibody's natural environment will not be present.Ordinarily, however, isolated antibody will be prepared by at least onepurification step.

The word “label” when used herein refers to a detectable compound orcomposition which is conjugated directly or indirectly to the antibodyso as to generate a “labeled” antibody. The label may be detectable byitself (e.g. radioisotope labels or fluorescent labels) or, in the caseof an enzymatic label, may catalyze chemical alteration of a substratecompound or composition which is detectable.

By “solid phase” is meant a non-aqueous matrix to which the antibody ofthe present invention can adhere. Examples of solid phases encompassedherein include those formed partially or entirely of glass (e.g.,controlled pore glass), polysaccharides (e.g., agarose),polyacrylamides, polystyrene, polyvinyl alcohol and silicones. Incertain embodiments, depending on the context, the solid phase cancomprise the well of an assay plate; in others it is a purificationcolumn (e.g., an affinity chromatography column). This term alsoincludes a discontinuous solid phase of discrete particles, such asthose described in U.S. Pat. No. 4,275,149.

A “liposome” is a small vesicle composed of various types of lipids,phospholipids and/or surfactant which is useful for delivery of a drug(such as a PRO polypeptide or antibody thereto) to a mammal. Thecomponents of the liposome are commonly arranged in a bilayer formation,similar to the lipid arrangement of biological membranes.

A “small molecule” is defined herein to have a molecular weight belowabout 500 Daltons.

TABLE 1 /*  *  * C-C increased from 12 to 15  * Z is average of EQ  * Bis average of ND  * match with stop is _M; stop−stop = 0; J (joker)match = 0  */ #define _M −8 /* value of a match with a stop */ int_day[26][26] = { /* A B C D E F G H I J K L M N O P Q R S T U V W X Y Z*/ /* A */ { 2, 0,−2, 0, 0,−4, 1,−1,−1, 0,−1,−2,−1, 0,_M, 1, 0,−2, 1, 1,0, 0,−6, 0,−3, 0}, /* B */ { 0, 3,−4, 3, 2,−5, 0, 1,−2, 0, 0,−3,−2,2,_M,−1, 1, 0, 0, 0, 0,−2,−5, 0,−3, 1}, /* C */{−2,−4,15,−5,−5,−4,−3,−3,−2, 0,−5,−6,−5,−4,_M,−3,−5,−4, 0,−2, 0,−2,−8,0, 0,−5}, /* D */ { 0, 3,−5, 4, 3,−6, 1, 1,−2, 0, 0,−4,−3, 2,_M,−1,2,−1, 0, 0, 0,−2,−7, 0,−4, 2}, /* E */ { 0, 2,−5, 3, 4,−5, 0, 1,−2, 0,0,−3,−2, 1,_M,−1, 2,−1, 0, 0, 0,−2,−7, 0,−4, 3}, /* F */{−4,−5,−4,−6,−5, 9,−5,−2, 1, 0,−5, 2, 0,−4,_M,−5,−5,−4,−3,−3, 0,−1, 0,0, 7,−5}, /* G */ { 1, 0,−3, 1, 0,−5, 5,−2,−3, 0,−2,−4,−3,0,_M,−1,−1,−3, 1, 0, 0,−1,−7, 0,−5, 0}, /* H */ {−1, 1,−3, 1, 1,−2,−2,6,−2, 0, 0,−2,−2, 2,_M, 0, 3, 2,−1,−1, 0,−2,−3, 0, 0, 2}, /* I */{−1,−2,−2,−2,−2, 1,−3,−2, 5, 0,−2, 2, 2,−2,_M,−2,−2,−2,−1, 0, 0, 4,−5,0,−1,−2}, /* J */ { 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0,_M, 0, 0,0, 0, 0, 0, 0, 0, 0, 0, 0}, /* K */ {−1, 0,−5, 0, 0,−5,−2, 0,−2, 0,5,−3, 0, 1,_M,−1, 1, 3, 0, 0, 0,−2,−3, 0,−4, 0}, /* L */{−2,−3,−6,−4,−3, 2,−4,−2, 2, 0,−3, 6, 4,−3,_M,−3,−2,−3,−3,−1, 0, 2,−2,0,−1,−2}, /* M */ {−1,−2,−5,−3,−2, 0,−3,−2, 2, 0, 0, 4, 6,−2,_M,−2,−1,0,−2,−1, 0, 2,−4, 0,−2,−1}, /* N */ { 0, 2,−4, 2, 1,−4, 0, 2,−2, 0,1,−3,−2, 2,_M,−1, 1, 0, 1, 0, 0,−2,−4, 0,−2, 1}, /* O */{_M,_M,_M,_M,_M,_M,_M,_M,_M,_M,_M,_M,_M,_M,0,_M,_M,_M,_M,_M,_M,_M,_M,_M,_M,_M,}, /* P */ { 1,−1,−3,−1,−1,−5,−1,0,−2, 0,−1,−3,−2,−1,_M, 6, 0, 0, 1, 0, 0,−1,−6, 0,−5, 0}, /* Q */ { 0,1,−5, 2, 2,−5,−1, 3,−2, 0, 1,−2,−1, 1,_M, 0, 4, 1,−1,−1, 0,−2,−5, 0,−4,3}, /* R */ {−2, 0,−4,−1,−1,−4,−3, 2,−2, 0, 3,−3, 0, 0,_M, 0, 1, 6,0,−1, 0,−2, 2, 0,−4, 0}, /* S */ { 1, 0, 0, 0, 0,−3, 1,−1,−1, 0,0,−3,−2, 1,_M, 1,−1, 0, 2, 1, 0,−1,−2, 0,−3, 0}, /* T */ { 1, 0,−2, 0,0,−3, 0,−1, 0, 0, 0,−1,−1, 0,_M, 0,−1,−1, 1, 3, 0, 0,−5, 0,−3, 0}, /* U*/ { 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0,_M, 0, 0, 0, 0, 0, 0, 0,0, 0, 0, 0}, /* V */ { 0,−2,−2,−2,−2,−1,−1,−2, 4, 0,−2, 2,2,−2,_M,−1,−2,−2,−1, 0, 0, 4,−6, 0,−2,−2}, /* W */ {−6,−5,−8,−7,−7,0,−7,−3,−5, 0,−3,−2,−4,−4,_M,−6,−5, 2,−2,−5, 0,−6,17, 0, 0,−6}, /* X */{ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0,_M, 0, 0, 0, 0, 0, 0, 0, 0,0, 0, 0}, /* Y */ {−3,−3, 0,−4,−4, 7,−5, 0,−1,0,−4,−1,−2,−2,_M,−5,−4,−4,−3,−3, 0,−2, 0, 0,10,−4}, /* Z */ { 0, 1,−5,2, 3,−5, 0, 2,−2, 0, 0,−2,−1, 1,_M, 0, 3, 0, 0, 0, 0,−2,−6, 0,−4, 4} };/*  */ #include <stdio.h> #include <ctype.h> #define MAXJMP 16 /* maxjumps in a diag */ #deflne MAXGAP 24 /* don't continue to penalize gapslarger than this */ #define JMPS 1024 /* max jmps in an path */ #defineMX 4 /* save if there's at least MX-1 bases since last jmp */ #defineDMAT 3 /* value of matching bases */ #define DMIS 0 /* penalty formismatched bases */ #define DINS0 8 /* penalty for a gap */ #defineDINS1 1 /* penalty per base */ #define PINS0 8 /* penalty for a gap */#define PINS1 4 /* penalty per residue */ struct jmp { short n[MAXJMP];/* size of jmp (neg for dely) */ unsigned short x[MAXJMP]; /* base no.of jmp in seq x */ }; /* limits seq to 2{circumflex over ( )}16 −1 */struct diag { int score; /* score at last jmp */ long offset; /* offsetof prev block */ short ijmp; /* current jmp index */ struct jmp jp; /*list of jmps */ }; struct path { int spc; /* number of leading spaces */short n[JMPS]; /* size of jmp (gap) */ int x[JMPS]; /* loc of jmp (lastelem before gap) */ }; char *ofile; /* output file name */ char*namex[2]; /* seq names: getseqs() */ char *prog; /* prog name for errmsgs */ char *seqx[2]; /* seqs: getseqs() */ int dmax; /* best diag:nw() */ int dmax0; /* final diag */ int dna; /* set if dna: main() */int endgaps; /* set if penalizing end gaps */ int gapx, gapy; /* totalgaps in seqs */ int len0, len1; /* seq lens */ int ngapx, ngapy; /*total size of gaps */ int smax; /* max score: nw() */ int *xbm; /*bitmap for matching */ long offset; /* current offset in jmp file */struct diag *dx; /* holds diagonals */ struct path pp[2]; /* holds pathfor seqs */ char *calloc(), *malloc(), *index(), *strcpy(); char*getseq(), *g_calloc(); /* Needleman-Wunsch alignment program  *  *usage: progs file1 file2  * where file1 and file2 are two dna or twoprotein sequences.  * The sequences can be in upper- or lower-case anmay contain ambiguity  * Any lines beginning with ‘;’, ‘>’ or ‘<’ areignored  * Max file length is 65535 (limited by unsigned short x in thejmp struct)  * A sequence with 1/3 or more of its elements ACGTU isassumed to be DNA  * Output is in the file “align.out”  *  * The programmay create a tmp file in /tmp to hold info about traceback.  * Originalversion developed under BSD 4.3 on a vax 8650  */ #include “nw.h”#include “day.h” static _dbval[26] = {1,14,2,13,0,0,4,11,0,0,12,0,3,15,0,0,0,5,6,8,8,7,9,0,10,0 }; static_pbval[26] = { 1,2|(1<<(‘D’−‘A’))|(1<<(‘N’−‘A’)), 4, 8, 16, 32, 64, 128,256, 0xFFFFFFF, 1<<10, 1<<11, 1<<12, 1<<13, 1<<14, 1<<15, 1<<16, 1<<17,1<<18, 1<<19, 1<<20, 1<<21, 1<<22, 1<<23, 1<<24,1<<25|(1<<(‘E’−‘A‘))|(1<<(‘Q’−‘A’)) }; main(ac, av) main int ac; char*av[]; { prog = av[0]; if (ac != 3) { fprintf(stderr,“usage: %s file1file2\n”, prog); fprintf(stderr,“where file1 and file2 are two dna ortwo protein sequences.\n”); fprintf(stderr,“The sequences can be inupper- or lower-case\n”); fprintf(stderr,“Any lines beginning with ‘;’or‘<’are ignored\n”); fprintf(stderr,“Output is in the file\“align.out\”\n”); exit(1); } namex[0]= av[1]; namex[1]= av[2]; seqx[0]=getseq(namex[0], &len0); seqx[1]= getseq(namex[1], &len1); xbm =(dna)?_dbval : _pbval; endgaps = 0; /* 1 to penalize endgaps */ ofile =“align.out”; /* output file */ nw(); /* fill in the matrix, get thepossible jmps */ readjmps(); /* get the actual jmps */ print(); /* printstats, alignment */ cleanup(0); /* unlink any tmp files */ } /* do thealignment, return best score: main()  * dna: values in Fitch and Smith,PNAS, 80, 1382–1386, 1983  * pro: PAM 250 values  * When scores areequal, we prefer mismatches to any gap, prefer  * a new gap to extendingan ongoing gap, and prefer a gap in seqx  * to a gap in seq y.  */ nw()nw { char *px, *py; /* seqs and ptrs */ int *ndely, *dely; /* keep trackof dely */ int ndelx, delx; /* keep track of delx */ int *tmp; /* forswapping row0, row1 */ int mis; /* score for each type */ int ins0,ins1; /* insertion penalties */ register id; /* diagonal index */register ij; /* jmp index */ register *col0, *col1; /* score for curr,last row */ register xx, yy; /* index into seqs */ dx = (struct diag*)g_calloc(“to get diags”, len0+len1+1, sizeof(struct diag)); ndely =(int *)g_calloc(“to get dely”, len1+1, sizeof(int)); dely = (int*)g_calloc(“to get dely”, len1+1, sizeof(int)); col0 = (int*)g_calloc(“to get col0”, len1+1, sizeof(int)); col1 = (int*)g_calloc(“to get col1”, len1+1, sizeof(int)); ins0 = (dna)? DINS0 :PINS0; ins1 = (dna)? DINS1 : PINS1; smax = −10000; if (endgaps) { for(col0[0] = dely[0] = −ins0, yy = 1; yy <= len1; yy++) { col0[yy] =dely[yy] = col0[yy−1] − ins1; ndely[yy] = yy; } col0[0] = 0; /* WatermanBull Math Biol 84 */ } else for (yy = 1; yy <= len1; yy++) dely[yy] =−ins0; /* fill in match matrix  */ for (px = seqx[0], xx = 1; xx <=len0; px++, xx++) { /* initialize first entry in col  */ if (endgaps) {if(xx == 1) col1[0] = delx = −(ins0+ins1); else col1[0] = delx = col0[0]− ins1; ndelx = xx; } else { col1[0] = 0; delx = −ins0; ndelx = 0; }...nw for (py = seqx[1],yy = 1;yy <= len1;py++,yy++) { mis = col0[yy−1];if (dna) mis += (xbm[*px−‘A’]&xbm[*py−‘A’])? DMAT DMIS; else mis +=_day[*px−‘A’][*py−‘A’]; /* update penalty for del in x seq;  * favor newdel over ongong del  * ignore MAXGAP if weighting endgaps  */ if(endgaps || ndely[yy] < MAXGAP) { if (col0[yy] − ins0 >= dely[yy]) {dely[yy] = col0[yy] − (ins0+ins1); ndely[yy] = 1; }else { dely[yy] −=ins1; ndely[yy]++; } }else { if (col0[yy] − (ins0+ins1) >= dely[yy]) {dely[yy] = col0[yy] − (ins0+ins1); ndely[yy] = 1; }else ndely[yy]++; }/* update penalty for del in y seq;  * favor new del over ongong del  */if (endgaps || ndelx < MAXGAP) { if (col1[yy−1] − ins0 >= delx) { delx =col1[yy−1] − (ins0+ins1); ndelx = 1; }else{ delx −= ins1; ndelx++; }}else { if (col1[yy−1] − (ins0+ins1) >= delx) { delx = col1[yy−1] −(ins0+ins1); ndelx = 1; }else ndelx++; } /* pick the maximum score;we're favoring  * mis over any del and delx over dely  */ ...nw id = xx− yy + len1 − 1; if (mis >= delx && mis >= dely[yy]) col1[yy] = mis;else if (delx >= dely[yy]) { col1[yy] = delx; ij = dx[id].ijmp; if(dx[id].jp.n[0]&& (!dna || (ndelx >= MAXJMP && xx>dx[id].jp.x[ij]+MX) ||mis > dx[id].score+DINS0)) { dx[id].ijmp++; if (++ij >= MAXJMP) {writejmps(id); ij = dx[id].ijmp = 0; dx[id].offset = offset; offset +=sizeof(struct jmp) + sizeof(offset); } } dx[id].jp.n[ij]= ndelx;dx[id].jp.x[ij]= xx; dx[id].score = delx; } else { col1[yy] = dely[yy];ij = dx[id].ijmp; if (dx[id].jp.n[0] && (!dna || (ndely[yy] >= MAXJMP &&xx> dx[id].jp.x[ij]+MX) || mis > dx[id].score+DINS0)) { dx[id].ijmp++;if (++ij >= MAXJMP){ writejmps(id); ij = dx[id].ijmp = 0; dx[id].offset= offset; offset += sizeof(struct jmp) + sizeof(offset); } }dx[id].jp.n[ij] = −ndely[yy]; dx[id].jp.x[ij] = xx; dx[id].score =dely[yy]; } if (xx == len0 && yy < len1) { /* last col  */ if (endgaps)col1[yy] −= ins0+ins1*(len1−yy); if (col1[yy]> smax) { smax = col1[yy];dmax = id; } } } if (endgaps && xx < len0) col1[yy−1] −=ins0+ins1*(1en0−xx); if (col1[yy−1] > smax) { smax = col1[yy−1]; dmax =id; } tmp = col0; col0 = col1; col1 = tmp; } (void) free((char *)ndely);(void) free((char *)dely); (void) free((char *)col0); (void) free((char*)col1); } /*  *  * print() -- only routine visible outside this module *  * static:  * getmat() -- trace back best path, count matches:print()  * pr_align() -- print alignment of described in array p[]:pint()  * dumpblock() -- dump a block of lines with numbers, stars:pr_align()  * nums() -- put out a number line: dumpblock()  * putline()-- put out a line (name, [num], seq, [num]): dumpblock()  * stars() --put a line of stars: dumpblock()  * stripname() -- strip any path andprefix from a seqname  */ #include “nw.h” #define SPC 3 #define P_LINE256 /* maximum output line */ #define P_SPC 3 /* space between name ornum and seq */ extern _day[26][26]; int olen; /* set output line length*/ FILE *fx; /* output file */ print() print { int lx, ly, firstgap,lastgap; /* overlap */ if ((fx = fopen(ofile, “w”)) == 0) {fprintf(stderr,“%s: can't write %s\n”, prog, ofile); cleanup(1); }fprintf(fx, “<first sequence: %s (length = %d)\n”, namex[0], len0);fprintf(fx, “<second sequence: %s (length = %d)\n”, namex[1], len1);olen = 60; 1x = len0; 1y = len1; firstgap = lastgap = 0; if(dmax < len1− 1) { /* leading gap in x */ pp[0].spc = firstgap = len1 − dmax − 1; 1y−= pp[0].spc; } else if (dmax > len1 − 1) { /* leading gap in y */pp[1].spc = firstgap = dmax − (len1 − 1); 1x −= pp[1].spc; } if(dmax0 <len0 − 1) { /* trailing gap in x */ lastgap = len0 − dmax0 − 1; 1x −=lastgap; } else if(dmax0 > len0 − 1) { /* trailing gap in y */ lastgap =dmax0 − (len0 − 1); 1y −= lastgap; } getmat(1x, 1y, firstgap, lastgap);pr_align(); } /*  * trace back the best path, count matches  */ staticgetmat(1x, 1y, firstgap, lastgap) getmat int 1x, 1y; /* “core”(minusendgaps) */ int firstgap, lastgap; /* leading trailing overlap */ { intnm, i0, i1, siz0, siz1; char outx[32]; double pct; register n0, n1;register char *p0, *p1; /* get total matches, score  */ i0 = i1 = siz0 =siz1 = 0; p0 = seqx[0] + pp[1].spc; p1 = seqx[1] + pp[0].spc; n0 =pp[1].spc + 1; n1 = pp[0].spc + 1; nm = 0; while ( *p0 && *p1 ) { if(siz0) { p1 ++; n1 ++; siz0−−; } else if (siz1) { p0++; n0++; siz1−−; }else { if (xbm[*p0−‘A’]&xbm[*p1−‘A’]) nm++; if (n0++ == pp[0].x[i0])siz0 = pp[0].n[i0++]; if (n1++== pp[1].x[i1]) siz1 = pp[1].n[i1++];p0++; p1++; } } /* pct homology:  * if penalizing endgaps, base is theshorter seq  * else, knock off overhangs and take shorter core  */ if(endgaps) 1x = (len0 < len1)? len0 : len1; else 1x = (1x < 1y)? 1x: 1y;pct = 100.*(double)nm/(double)1x; fprintf(fx, “\n”); fprintf(fx, “< %dmatch%s in an overlap of %d: %.2f percent similarity\n”, nm, (nm ==1)?“” : “es”, 1x, pct); fprintf(fx, “<gaps in first sequence: %d”, gapx);...getmat if (gapx) { (void) sprintf(outx, “ (%d %s%s)”, ngapx, (dna)?“base”:“residue”, (ngapx == 1)? “”:“s”); fprintf(fx,“%s”, outx);fprintf(fx, “,gaps in second sequence: %d”, gapy); if (gapy) { (void)sprintf(outx, “ (%d %s%s)”, ngapy, (dna)? “base”:“residue”, (ngapy ==1)? “”:“s”); fprintf(fx,“%s”, outx); } if (dna) fprintf(fx, “\n<score:%d (match % = %d, mismatch = %d, gap penalty = %d + %d per base)\n”,smax, DMAT, DMIS, DINS0, DINS1); else fprintf(fx, “\n<score: %d (DayhoffPAM 250 matrix, gap penalty = %d + %d per residue)\n”, smax, PINS0,PINS1); if (endgaps) fprintf(fx, “<endgaps penalized. left endgap: %d%s%s, right endgap: %d %s%s\n”, firstgap, (dna)? “base”: “residue”,(firstgap == 1)? “”: “s”, lastgap, (dna)? “base”: “residue”, (lastgap ==1)? “”: “s”); else fprintf(fx, “<endgaps not penalized\n”); } static nm;/* matches in core -- for checking */ static lmax; /* lengths ofstripped file names */ static ij[2]; /* jmp index for a path */ staticnc[2]; /* number at start of current line */ static ni[2]; /* currentelem number -- for gapping */ static siz[2]; static char *ps[2]; /* ptrto current element */ static char *po[2]; /* ptr to next output charslot */ static char out[2][P_LINE]; /* output line */ static charstar[P_LINE]; /* set by stars() */ /*  * print alignment of described instruct path pp[]  */ static pr_align() pr_align { int nn; /* char count*/ int more; register i; for(i = 0, lmax = 0; i < 2; i++){ nn =stripname(namex[i]); if(nn > lmax) lmax = nn; nc[i] = 1; ni[i] = 1;siz[i] = ij[i] = 0; ps[i] = seqx[i]; po[i] = out[i]; } for (nn = nm = 0,more = 1; more; ) { ...pr_align for (i = more = 0; i < 2; i++) { /*  *do we have more of this sequence?  */ if (!*ps[i]) continue; more++; if(pp[i].spc) { /* leading space */ *po[i]++ = ‘ ’; pp[i].sp−−; } else if(siz[i]) { /* in a gap */ *po[i]++ = ‘−’; siz[i]−−; } else { /* we'reputting a seq element  */ *po[i] = *ps[i]; if (islower(*ps[i])) *ps[i] =toupper(*ps[i]); po[i]++; ps[i]++; /*  * are we at next gap for thisseq? */ if (ni[i] == pp[i].x[ij[i]]) { /*  * we need to merge all gaps * at this location  */ siz[i] = pp[i].n[ij[i]++]; while (ni[i] ==pp[i].x[ij]]) siz[i] += pp[i].n[ij[i]++]; } ni[i]++; } } if([++nn ==olen|| !more && nn) { dumpblock(); for (i = 0; i < 2; i++) po[i] = out[i];nn = 0; } } } /*  * dump a block of lines, including numbers, stars:pr_align()  */ static dumpblock() dumpblock { register i; for(i = 0; i <2; i++) *po[i]−− = ‘\0’; ...dumpblock (void) putc(‘\n’, fx); for (i = 0;i < 2; i++) { if (*out[i]&& (*out[i] != ‘ ’ || *(po[i]) != ‘ ’)) { if (i==0) nums(i); if (i == 0 && *out[1]) stars(); putline(i); if (i == 0 &&*out[1]) fprintf(fx, star); if (i == 1) nums(i); } } } /*  * put out anumber line: dumpblock()  */ static nums(ix) nums int ix; /* index inout[]holding seq line */ { char nline[P_LINE]; register i, j; registerchar *pn, *px, *py; for (pn = nline, i = 0;i < lmax+P_SPC; i++,pn++) *pn= ‘ ’; for (i = nc[ix], py = out[ix]; *py; py++, pn++) { if (*py == ‘ ’|| *py == ‘−’) *pn = ‘ ’; else { if (i%10 == 0 || (i == 1 && nc[ix] !=1)) { j = (i < 0)?−i : i; for (px = pn; j; j /= 10,px−−) *px = j%10 +‘0’; if (i < 0) *px = ‘−’; } else *pn = ‘ ’; i++; } } *pn = ‘\0’; *nc[ix] =i for (pn = nline; *pn; pn++) (void) putc(*pn, fx); (void)putc(‘\n’, fx); } /*  * put out a line (name, [num], seq, [num]):dumpblock()  */ static putline(ix) putline int ix; { ...putline int i;register char *px; for (px = namex[ix], i = 0; *px && *px != ‘:’; px++,i++) (void) putc(*px, fx); for(; i < lmax+P_SPC; i++) (void) putc(‘ ’,fx); /* these count from 1:  * ni[]is current element (from 1)  * nc[]isnumber at start of current line  */ for (px = out[ix]; *px; px++) (void)putc(*px&0x7F, fx); (void) putc(‘\n’, fx); } /*  * put a line of stars(seqs always in out[0], out[1]): dumpblock()  */ static stars() stars {int i; register char *p0, *p1, cx, *px; if (!*out[0] || (*out[0] == ‘ ’&& *(po[0]) == ‘ ’) ||   !*out[1] || (*out[1] == ‘ ’ && *(po[1]) == ‘’)) return; px = star; for (i = lmax+P_SPC; i; i−−) *px++ = ‘ ’; for (p0= out[0],p1 = out[1]; *p0 && *p1; p0++,p1++) { if (isalpha(*p0) &&isalpha(*p1)) { if (xbm[*p0−‘A’]&xbm[*p1−‘A’]) { cx = ‘*’; nm++; } elseif (!dna &&_day[*p0−‘A’ [*p1−‘A’] >0) cx = ‘−’; else cx = ‘ ’; } else cx= ‘ ’; *px++ = cx; } *px++ = ‘\n’; *px = ‘\0’; } /*  * strip path orprefix from pn, return len: pr_align()  */ static stripname(pn)Stripname char *pn; /* file name (may be path) */ { register char *px,*py; py = 0; for (px = pn; *px; px++) if (*px ==‘/’) py = px + 1; if(py) (void) strcpy(pn, py); return(strlen(pn)); } /*  * cleanup() --cleanup any tmp file  * getseq() -- read in seq. set dna, len, maxlen  *g calloc() -- calloc() with error checkin  * readjmps() -- get the goodjmps, from tmp file if necessary  * writejmps() -- write a filled arrayof jmps to a tmp file: nw()  */ #inclnde “nw.h” #include <sys/file.h>char *jname = “/tmp/homgXXXXXX”; /* tmp file for jmps */ FILE *fj; intcleanup(); /* cleanup tmp file */ long lseek(); /*  * remove any tmpfile if we blow  */ cleanup(i) cleanup int i; { if (fj) (void)unlink(jname); exit(i); } /*  * read, return ptr to seq, set dna, len,maxlen  * skip lines starting with ‘;’, ‘<’, or ‘>’  * seq in upper orlower case  */ char * getseq(file, len) getseq char *file; /* file name*/ int *len; /* seq len */ { char line[1024], *pseq; register char *px,*py; int natgc, tlen; FILE *fp; if ((fp = fopen(file,“r”)) == 0) {fprintf(stderr,“%s: can't read %s\n”, prog, file); exit(1); } tlen =natgc = 0; while (fgets(line, 1024, fp)) { if (*line == ‘;’ || *line ==‘<’ || *line == ‘>’) continue; for (px = line; *px != ‘\n’; px++) if(isupper(*px) || islower(*px)) tlen++; } if ((pseq =malloc((unsigned)(tlen+6))) == 0) { fprintf(stderr,“%s: malloc() failedto get %d bytes for %s\n”, prog, tlen+6, file); exit(1); } pseq[0] =pseq[1] = pseq[2] = pseq[3] = ‘\0’; ...getseq py = pseq + 4; *len =tlen; rewind(fp); while (fgets(line, 1024, fp)) { if(*line == ‘;’ ||*line == ‘<’ || *line == ‘>’) continue; for (px = line; *px != ‘\n’;px++) { if (isupper(*px)) *py++ = *px; else if (islower(*px)) *py ++ =toupper(*px); if (index(“ATGCU”,*(py−1))) natgc++; } } *py ++ = ‘\0’;*py = ‘\0’; (void) fclose(fp); dna = natgc > (tlen/3); return(pseq+4); }char * g_calloc(msg, nx, sz) g_calloc char *msg; /* program, callingroutine */ int nx, sz; /* number and size of elements */ { char *px,*calloc(); if ((px = calloc((unsigned)nx, (unsigned)sz)) == 0) { if(*msg) { fprintf(stderr, “%s: g_calloc() failed %s (n= %d, sz= %d)\n”,prog, msg, nx, sz); exit(1); } } return(px); } /*  * get final jmps fromdx[]or tmp file, set pp[], reset dmax: main()  */ readjmps() readjmps {int fd= −1; int siz, i0, i1; register i, j, xx; if (fj) { (void)fclose(fj); if ((fd = open(jname, O_RDONLY, 0)) < 0) { fprintf(stderr,“%s: Can't open() %s\n”, prog, jname); cleanup(1); } } for(i = i0 = i1 =0, dmax0 = dmax, xx = len0; ; i++) { while (1) { for (j = dx[dmax].ijmp;j >= 0 && dx[dmax].jp.x[j] >= xx; j−−) ; ..readjmps if(j < 0 &&dx[dmax].offset && fj) { (void) lseek(fd, dx[dmax].offset, 0); (void)read(fd, (char *)&dx[dmax].jp, sizeof(struct jmp)); (void) read(fd,(char *)&dx[dmax].offset, sizeof(dx[dmax].offset)); dx[dmax].ijmp =MAXJMP−1; } else break; } if (i >= JMPS) { fprintf(stderr, “%s: too manygaps in alignment\n”, prog); cleanup(1); } if(j >= 0) { siz =dx[dmax].jp.n[j]; xx = dx[dmax].jp.x[j]; dmax += siz; if (siz < 0) { /*gap in second seq */ pp[1].n[i1] = −siz; xx += siz; /* id = xx − yy +len1 − 1  */ pp[1].x[i1] = xx − dmax + len1 − 1; gapy ++; ngapy −= siz;/* ignore MAXGAP when doing endgaps */ siz = (−siz < MAXGAP || endgaps)?−siz : MAXGAP; i1++; } else if (siz > 0) { /* gap in first seq */pp[0].n[i0] = siz; pp[0].x[i0] = xx; gapx++; ngapx += siz; /* ignoreMAXGAP when doing endgaps */ siz (siz < MAXGAP || endgaps)? siz :MAXGAP; i0++; } } else break; } /* reverse the order of jmps  */ for (j= 0, i0−−; j < i0; j++, i0−−) { i = pp[0].n[j]; pp[0].n[j] =pp[0].n[i0]; pp[0].n[i0] = i i = pp[0].x[j]; pp[0].x[j] = pp[0].x[i0];pp[0].x[i0] = i } for (j = 0, i1−−; j < i1; j++, i1−−) { i = pp[1].n[j];pp[1].n[j] = pp[1].n[i1]; pp[1].n[i1] = i i = pp[1].x[j]; pp[1].x[j] =pp[1].x[i1]; pp[1].x[i1] = i } if (fd >= 0) (void) close(fd); if (fj) {(void) unlink(jname); fj = 0; offset = 0; } } /*  * write a filled jmpstruct offset of the prev one (if any): nw()  */ writejmps(ix) writejmpsint ix; { char *mktemp(); if (!fj) { if (mktemp(jname) < 0) {fprintf(stderr, “%s: can't mktemp() %s\n”, prog, jname); cleanup(1); }if ((fj = fopen(jname, “w”)) == 0) { fprintf(stderr, “%s: can't write%sn”, prog, jname); exit(1); } } (void) fwrite((char *)&dx[ix].jp,sizeof(struct jmp), 1, fj); (void) fwrite((char *)&dx[ix].offset,sizeof(dx[ix].offset), 1, fj); }

TABLE 2 PRO XXXXXXXXXXXXXXX (Length = 15 amino acids) ComparisonXXXXXYYYYYYY (Length = 12 amino acids) Protein% amino acid sequence identity=(the number of identically matching aminoacid residues between the two polypeptide sequences as determined byALIGN-2) divided by (the total number of amino acid residues of the PROpolypeptide)=5 divided by 15=33.3%

TABLE 3 PRO XXXXXXXXXX (Length = 10 amino acids) ComparisonXXXXXYYYYYYZZYZ (Length = 15 amino acids) Protein% amino acid sequence identity=(the number of identically matching aminoacid residues between the two polypeptide sequences as determined byALIGN-2) divided by (the total number of amino acid residues of the PROpolypeptide)=5 divided by 10=50%

TABLE 4 PRO-DNA NNNNNNNNNNNNNN (Length = 14 nucleotides) ComparisonNNNNNNLLLLLLLLLL (Length = 16 nucleotides) DNA% nucleic acid sequence identity=(the number of identically matchingnucleotides between the two nucleic acid sequences as determined byALIGN-2) divided by (the total number of nucleotides of the PRO-DNAnucleic acid sequence)=6 divided by 14=42.9%

TABLE 5 PRO-DNA NNNNNNNNNNNN (Length = 12 nucleotides) Comparison DNANNNNLLLVV (Length = 9 nucleotides)% nucleic acid sequence identity=(the number of identically matchingnucleotides between the two nucleic acid sequences as determined byALIGN-2) divided by (the total number of nucleotides of the PRO-DNAnucleic acid sequence)=4 divided by 12=33.3%II. Compositions and Methods of the Invention

A. Full-Length PRO Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO polypeptides. In particular, cDNAs encoding various PROpolypeptides have been identified and isolated, as disclosed in furtherdetail in the Examples below. It is noted that proteins produced inseparate expression rounds may be given different PRO numbers but theUNQ number is unique for any given DNA and the encoded protein, and willnot be changed. However, for sake of simplicity, in the presentspecification the protein encoded by the full length native nucleic acidmolecules disclosed herein as well as all further native homologues andvariants included in the foregoing definition of PRO, will be referredto as “PRO/number”, regardless of their origin or mode of preparation.

As disclosed in the Examples below, various cDNA clones have beendeposited with the ATCC. The actual nucleotide sequences of those clonescan readily be determined by the skilled artisan by sequencing of thedeposited clone using routine methods in the art. The predicted aminoacid sequence can be determined from the nucleotide sequence usingroutine skill. For the PRO polypeptides and encoding nucleic acidsdescribed herein, Applicants have identified what is believed to be thereading frame best identifiable with the sequence information availableat the time.

1. Full-Length PRO281 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO281 (UNQ244). In particular, cDNA encoding a PRO281 polypeptidehas been identified and isolated, as disclosed in further detail in theExamples below.

Using the WU-BLAST-2 sequence alignment computer program, it has beenfound that a full-length native sequence PRO281 (shown in FIG. 2 and SEQID NO:2) has certain amino acid sequence identity with the rat TEGTprotein. Accordingly, it is presently believed that PRO281 disclosed inthe present application is a newly identified TEGT homolog and maypossess activity typical of that protein.

2. Full-Length PRO276 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO276 (UNQ243). In particular, cDNA encoding a PRO276 polypeptidehas been identified and isolated, as disclosed in further detail in theExamples below.

As far as is known, the DNA16435-1208 sequence encodes a novel factordesignated herein as PRO276; using WU-BLAST-2 sequence alignmentcomputer programs, no significant sequence identities to any knownproteins were revealed. The sequence identity identifications which werefound are listed below in the examples.

3. Full-Length PRO189 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO189. In particular, Applicants have identified and isolated cDNAencoding a PRO189 polypeptide, as disclosed in further detail in theExamples below. To Applicants present knowledge, the DNA21624-1391nucleotide sequence encodes a novel factor; using BLAST and FastAsequence alignment computer programs, no significant sequence identitiesto any known proteins were revealed.

4. Full-Length PRO190 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO190. In particular, Applicants have identified and isolated cDNAencoding a PRO190 polypeptide, as disclosed in further detail in theExamples below. The PRO190-encoding clone was isolated from a humanretina library. To Applicants present knowledge, the DNA23334-1392nucleotide sequence encodes a novel multiple transmembrane spanningprotein; using BLAST and FastA sequence alignment computer programs,there is some sequence identity with CMP-sialic acid and UDP-galactosetransporters, indicating that PRO190 may be related to transporter orthat PRO190 may be a novel transporter.

5. Full-Length PRO341 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO341 (UNQ300). In particular, cDNA encoding a PRO341 polypeptidehas been identified and isolated, as disclosed in further detail in theExamples below.

The DNA26288-1239 clone was isolated from a human placenta library. Asfar as is known, the DNA26288-1239 sequence encodes a novel factordesignated herein as PRO341; using the WU-BLAST-2 sequence alignmentcomputer program, no significant sequence identities to any knownproteins were revealed.

6. Full-Length PRO180 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO180 (UNQ154). In particular, cDNA encoding a PRO180 polypeptidehas been identified and isolated, as disclosed in further detail in theExamples below.

The DNA26843-1389 clone was isolated from a human placenta library usingoligos formed from DNA12922 isolated from an amylase screen. As far asis known, the DNA26843-1389 sequence encodes a novel factor designatedherein as PRO180.

7. Full-Length PRO194 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO194. In particular, Applicants have identified and isolated cDNAencoding a PRO194 polypeptide, as disclosed in further detail in theExamples below. The PRO194-encoding clone was isolated from a humanfetal lung library. To Applicants present knowledge, the DNA26844-1394nucleotide sequence encodes a novel factor; using BLAST and FastAsequence alignment computer programs, no significant sequence identitiesto any known proteins were revealed.

8. Full-Length PRO203 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO203. In particular, Applicants have identified and isolated cDNAencoding a PRO203 polypeptide, as disclosed in further detail in theExamples below. Using BLAST and FastA sequence alignment computerprograms, Applicants found that the PRO203 polypeptide has sequenceidentity with GST ATPase. Accordingly, it is presently believed thatPRO203 polypeptide disclosed in the present application is a newlyidentified member of the ATPase family and possesses activity typical ofthe GST ATPase.

9. Full-Length PRO290 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO290. In particular, cDNA encoding a PRO290 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 23 (SEQ ID NO:33), revealed sequence identities betweenthe PRO290 amino acid sequence and the following Dayhoffsequences:P_R99800, CC4H_HUMAN, YCS2_YEAST, CEF35G12₁₃ 13, HSFAN_(—)1,MMU52461_(—)1, MMU70015_(—)1, HSU67615_(—)1, CET01H10_(—)8 andCELT28F2_(—)6.

It is currently believed that PRO290 is an intracellular protein relatedto one or more of the above proteins.

10. Full-Length PRO874 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO874. In particular, Applicants have identified and isolated cDNAencoding a PRO874 polypeptide, as disclosed in further detail in theExamples below. The PRO874-encoding clone was isolated from a humanfetal lung library. To Applicants present knowledge, the DNA40621-1440nucleotide sequence encodes a novel factor. Although, using BLAST andFastA sequence alignment computer programs, some sequence identity withknown proteins was revealed.

11. Full-Length PRO710 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO710. In particular, Applicants have identified and isolated cDNAencoding a PRO710 polypeptide, as disclosed in further detail in theExamples below. Using BLAST and FastA sequence alignment computerprograms, Applicants found that the PRO710 polypeptide has significantsimilarity to the CDC45 protein. Accordingly, it is presently believedthat PRO710 polypeptide disclosed in the present application is a newlyidentified CDC45 homolog.

12. Full-Length PRO1151 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1151. In particular, cDNA encoding a PRO1151 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

Using the WU-BLAST-2 sequence alignment computer program, it has beenfound that a full-length native sequence PRO1151 (shown in FIG. 30 andSEQ ID NO:47) has certain amino acid sequence identity with the human 30kD adipocyte complement-related precursor protein (ACR3_HUMAN).Accordingly, it is presently believed that PRO1151 disclosed in thepresent application is a newly identified member of the complementprotein family and may possess activity typical of that family.

13. Full-Length PRO1282 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1282. In particular, cDNA encoding a PRO1282 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

As far as is known, the DNA45495-1550 sequence encodes a novel factordesignated herein as PRO1282. Using WU-BLAST-2 sequence alignmentcomputer programs, some sequence identities between PRO1282 and otherleucine rich repeat proteins were revealed, as discussed in the examplesbelow, indicating that a novel member of the leucine rich repeatsuperfamily has been identified.

14. Full-Length PRO358 Polypeptides

The present invention further provides newly identified and isolatednucleotide sequences encoding a polypeptide referred to in the presentapplication as PRO358. In particular, Applicants have identified andisolated cDNA encoding a novel human Toll polypeptide (PRO358), asdisclosed in further detail in the Examples below. Using BLAST and FastAsequence alignment computer programs, Applicants found that the codingsequence of PRO358 shows significant homology to DNA sequencesHSU88540_(—)1, HSU88878_(—)1, HSU88879_(—)1, HSU88880_(—)1,HS88881_(—)1, and HSU79260_(—)1 in the GenBank database. With theexception of HSU79260_(—)1, the noted proteins have been identified ashuman toll-like receptors.

Accordingly, it is presently believed that the PRO358 proteins disclosedin the present application are newly identified human homologues of theDrosophila protein Toll, and are likely to play an important role inadaptive immunity. More specifically, PRO358 may be involved ininflammation, septic shock, and response to pathogens, and play possibleroles in diverse medical conditions that are aggravated by immuneresponse, such as, for example, diabetes, ALS, cancer, rheumatoidarthritis, and ulcers. The role of PRO385 as pathogen patternrecognition receptors, sensing the presence of conserved molecularstructures present on microbes, is further supported by the datadisclosed in the present application, showing that a known humanToll-like receptor, TLR2 is a direct mediator of LPS signaling.

15. Full-Length PRO1310 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1310. In particular, cDNA encoding a PRO1310 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

Using WU-BLAST-2 sequence alignment computer programs, it has been foundthat a full-length native sequence PRO1310 (shown in FIG. 36 and SEQ IDNO:62) has certain amino acid sequence identity with carboxypeptidaseX2. Accordingly, it is presently believed that PRO1310 disclosed in thepresent application is a newly identified member of the carboxypeptidasefamily and may possess carboxyl end amino acid removal activity.

16. Full-Length PRO698 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO698. In particular, Applicants have identified and isolated cDNAencoding a PRO698 polypeptide, as disclosed in further detail in theExamples below. Using BLAST and FastA sequence alignment computerprograms, Applicants found that the PRO698 polypeptide has significantsimilarity to the olfactomedin protein. Accordingly, it is presentlybelieved that PRO698 polypeptide disclosed in the present applicationmay be a newly identified olfactomedin homolog.

17. Full-Length PRO732 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO732. In particular, Applicants have identified and isolated cDNAencoding a PRO732 polypeptide, as disclosed in further detail in theExamples below. Using BLAST and FastA sequence alignment computerprograms, Applicants found that the PRO732 polypeptide has significantsimilarity to the human placental Diff33 protein. Accordingly, it ispresently believed that PRO732 polypeptide disclosed in the presentapplication is a newly identified Diff33 homolog.

18. Full-Length PRO1120 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1120. In particular, cDNA encoding a PRO1120 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

Using WU-BLAST-2 sequence alignment computer programs, it has been foundthat a full-length native sequence PRO1120 (shown in FIG. 47 and SEQ IDNO:84) has certain amino acid sequence identity with the known sulfataseproteins designated CELK09C4_(—)1, and GL6S_HUMAN, respectively, in theDayhoff database (version 35.45 SwissProt 35). Accordingly, it ispresently believed that PRO1120 disclosed in the present application isa newly identified member of the sulfatase family and may possessactivity typical of sulfatases.

19. Full-Length PRO537 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO537. In particular, cDNA encoding a PRO537 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow. The DNA49141-1431 clone was isolated from a human placentalibrary using a trapping technique which selects for nucleotidesequences encoding secreted proteins. Thus, the DNA49141-1431 clone doesencode a secreted factor. As far as is known, the DNA49141-1431 sequenceencodes a novel factor designated herein as PRO537; using the WU-BLAST2sequence alignment computer program, no significant sequence identitiesto any known proteins were revealed.

20. Full-Length PRO536 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO536. In particular, cDNA encoding a PRO536 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

The DNA49142-1430 clone was isolated from a human infant brain libraryusing a trapping technique which selects for nucleotide sequencesencoding secreted proteins. Thus, the DNA49142-1430 clone does encode asecreted factor. As far as is known, the DNA49142-1430 sequence encodesa novel factor designated herein as PRO536; using the WU-BLAST-2sequence alignment computer program, no significant sequence identitiesto any known proteins were revealed.

21. Full-Length PRO535 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO535. In particular, cDNA encoding a PRO535 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

Using the WU-BLAST2 sequence alignment computer program, it has beenfound that a full-length native sequence PRO535 (shown in FIG. 53 andSEQ ID NO:99) has amino acid sequence identity with a putativepeptidyl-prolyl isomerase protein. Accordingly, it is presently believedthat PRO535 disclosed in the present application is a newly identifiedmember of the isomerase protein family and may possess activity typicalof those proteins.

22. Full-Length PRO718 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO718. In particular, Applicants have identified and isolated cDNAencoding a PRO718 polypeptide, as disclosed in further detail in theExamples below. The PRO718-encoding clone was isolated from a humanfetal lung library. To Applicants present knowledge, the DNA49647-1398nucleotide sequence encodes a novel factor; using BLAST and FastAsequence alignment computer programs, no significant sequence identitiesto any known proteins were revealed.

23. Full-Length PRO872 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO872. In particular, Applicants have identified and isolated cDNAencoding a PRO872 polypeptide, as disclosed in further detail in theExamples below. Using BLAST and FastA sequence alignment computerprograms, Applicants found that the PRO872 polypeptide has sequenceidentity with dehydrogenases. Accordingly, it is presently believed thatPRO872 polypeptide disclosed in the present application is a newlyidentified member of the dehydrogenase family and possessesdehydrogenase activity.

24. Full-Length PRO1063 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1063. In particular, Applicants have identified and isolated cDNAencoding a PRO1063 polypeptide, as disclosed in further detail in theExamples below. Using BLAST and FastA sequence alignment computerprograms, Applicants found that the PRO1063 polypeptide has significantsimilarity to the human type IV collagenase protein. Accordingly, it ispresently believed that PRO1063 polypeptide disclosed in the presentapplication is a newly identified collagenase homolog.

25. Full-Length PRO619 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO619. In particular, cDNA encoding a PRO619 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

Using WU-BLAST-2 sequence alignment computer program, it has been foundthat a full-length native sequence PRO619 (shown in FIG. 68 and SEQ IDNO:117) has certain amino acid sequence identity with VpreB3.Accordingly, it is presently believed that PRO619 disclosed in thepresent application is a newly identified member of the IgG superfamilyand may possess activity related to the assembly and/or components ofthe surrogate light chain associated with developing B cells.

26. Full-Length PRO943 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO943. In particular, cDNA encoding a PRO943 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

Using the WU-BLAST-2 sequence alignment computer program, it has beenfound that a full-length native sequence PRO943 (shown in FIG. 70 andSEQ ID NO:119) has amino acid sequence identity with the fibroblastgrowth factor receptor-4 protein. Accordingly, it is presently believedthat PRO943 disclosed in the present application is a newly identifiedmember of the fibroblast growth factor receptor family and may possessactivity typical of that family.

27. Full-Length PRO1188 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1188. In particular, cDNA encoding a PRO1188 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

As discussed in more detail in Example 1 below, using WU-BLAST-2sequence alignment computer programs, it has been found that afull-length native sequence PRO1188 (shown in FIG. 72; SEQ ID NO:124)has certain amino acid sequence identity with nucleotidepyrophosphohydrolase (SSU83114_(—)1). Accordingly, it is presentlybelieved that PRO1188 disclosed in the present application is a newlyidentified member of the nucleotide pyrophosphohydrolase family and maypossess activity typical of that family of proteins.

28. Full-Length PRO1133 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1133. In particular, cDNA encoding a PRO1133 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

Using WU-BLAST-2 sequence alignment computer programs, it has been foundthat a full-length native sequence PRO1133 (shown in FIG. 74 and SEQ IDNO:129) has certain amino acid sequence identity with netrin 1a, Dayhoffaccession AF002717_(—)1. Accordingly, it is presently believed thatPRO1133 disclosed in the present application shares at least one relatedmechanism with netrin.

29. Full-Length PRO784 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO784. In particular, cDNA, designated herein as “DNA53978-1443”,which encodes a PRO784 polypeptide, has been identified and isolated, asdisclosed in further detail in the Examples below.

Using BLAST and FastA sequence alignment computer programs, it has beenfound that a full-length native sequence PRO784 (shown in FIG. 76 andSEQ ID NO:135) has certain amino acid sequence identity with sec22homologs. Accordingly, it is presently believed that PRO784 disclosed inthe present application is a newly identified member of the sec22 familyand may possess vesicle trafficking activities typical of the sec22family.

30. Full-Length PRO783 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO783. In particular, Applicants have identified and isolated cDNAencoding a PRO783 polypeptide, as disclosed in further detail in theExamples below. The PRO783-encoding clone was isolated from a humanfetal kidney library. To Applicants present knowledge, the DNA53996-1442nucleotide sequence encodes a novel factor. However, using BLAST andFastA sequence alignment computer programs, some sequence identity toknown proteins was found.

31. Full-Length PRO820 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO820. In particular, Applicants have identified and isolated cDNAencoding a PRO820 polypeptide, as disclosed in further detail in theExamples below. Using BLAST and FastA sequence alignment computerprograms, Applicants found that various portions of the PRO820polypeptide have sequence identity with the low affinity immunoglobulingamma Fc receptor, the IgE high affinity Fc receptor and the highaffinity immunoglobulin epsilon receptor. Accordingly, it is presentlybelieved that PRO820 polypeptide disclosed in the present application isa newly identified member of the Fc receptor family.

32. Full-Length PRO1080 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1080. In particular, Applicants have identified and isolated cDNAencoding a PRO1080 polypeptide, as disclosed in further detail in theExamples below. Using BLAST and FastA sequence alignment computerprograms, Dayhoff database (version 35.45 SwissProt 35), Applicantsfound that the PRO1080 polypeptide has sequence identity with a 39.9 kdprotein designated as “YRY1_CAEEL”, a DnaJ homolog designated“AF027149_(—)5”, a DnaJ homolog 2 designated “RNU95727_(—)1”, andDna3/Cpr3 designated “AF011793_(—)1”. Accordingly, these resultsindicate that the PRO1080 polypeptide disclosed in the presentapplication may be a newly identified member of the DnaJ-like proteinfamily and therefore may be involved in protein biogenesis.

33. Full-Length PRO1079 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1079. In particular, cDNA encoding a PRO1079 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

As far as is known, the DNA56050-1455 sequence encodes a novel factordesignated herein as PRO1079. Although, using WU-BLAST2 sequencealignment computer programs, some sequence identities to known proteinswas revealed.

34. Full-Length PRO793 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO793. In particular, cDNA encoding a PRO793 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

The DNA56110-1437 clone was isolated from a human skin tumor library. Asfar as is known, the DNA56110-1437 sequence encodes a novel factordesignated herein as PRO793; using the WU-BLAST-2 sequence alignmentcomputer program, no significant sequence identities to any knownproteins were revealed.

35. Full-Length PRO1016 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1016. In particular, Applicants have identified and isolated cDNAencoding a PRO1016 polypeptide, as disclosed in further detail in theExamples below. Using BLAST and FastA sequence alignment computerprograms, Applicants found that various portions of the PRO1016polypeptide have sequence identity with acyltransferases. Accordingly,it is presently believed that PRO1016 polypeptide disclosed in thepresent application is a newly identified member of the acyltransferasefamily and possesses acyltalation capabilities typical of this family.

36. Full-Length PRO1013 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1013. In particular, Applicants have identified cDNA encoding aPRO1013 polypeptide, as disclosed in further detail in the Examplesbelow. The PRO1013-encoding clone came from a human breast tumor tissuelibrary. Thus, the PRO1013-encoding clone may encode a secreted factorrelated to cancer. To Applicants present knowledge, the DNA56410-1414nucleotide sequence encodes a novel factor. Using BLAST and FastAsequence alignment computer programs, some sequence identity withKIAA0157 and P120 was revealed. PRO1013 has at least one region incommon with growth factor and cytoline receptors.

37. Full-Length PRO937 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO937. In particular, Applicants have identified and isolated cDNAencoding a PRO937 polypeptide, as disclosed in further detail in theExamples below. Using BLAST and FastA sequence alignment computerprograms, Applicants found that the PRO937 polypeptide has significantsequence identity with members of the glypican family of proteins.Accordingly, it is presently believed that PRO937 polypeptide disclosedin the present application is a newly identified member of the glypicanfamily possesses properties typical of the glypican family.

38. Full-Length PRO842 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO842. In particular, cDNA encoding a PRO842 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

As far as is known, the DNA56855-1447 sequence encodes a novel secretedfactor designated herein as PRO842. However, using WU-BLAST2 sequencealignment computer programs, some sequence identity to any knownproteins were revealed.

39. Full-Length PRO839 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO839. In particular, cDNA encoding a PRO839 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

As far as is known, the DNA56859-1445 sequence encodes a novel factordesignated herein as PRO839. However, using WU-BLAST-2 sequencealignment computer programs, some sequence identities to known proteinswas revealed.

40. Full-Length PRO1180 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1180. In particular, Applicants have identified and isolated cDNAencoding a PRO1180 polypeptide, as disclosed in further detail in theExamples below. Using BLAST and FastA sequence alignment computerprograms, Applicants found that the PRO1180 polypeptide has significantsimilarity to methyltransferase enzymes. Accordingly, it is presentlybelieved that PRO1180 polypeptide disclosed in the present applicationis a newly identified member of the methyltransferase family andpossesses activity typical of that family.

41. Full-Length PRO1134 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1134. In particular, cDNA encoding a PRO1134 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

The DNA56865-1491 clone was isolated from a human fetal liver spleenlibrary using a trapping technique which selects for nucleotidesequences encoding secreted proteins. Thus, the DNA56865-1491 clone doesencode a secreted factor. As far as is known, the DNA56865-1491 sequenceencodes a novel factor designated herein as PRO1134; using the WU-BLAST2sequence alignment computer program, no significant sequence identitiesto any known proteins were revealed.

42. Full-Length PRO830 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO830. In particular, cDNA encoding a PRO830 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

The DNA56866-1342 clone was isolated from a human fetal liver/spleenlibrary using a trapping technique which selects for nucleotidesequences encoding secreted proteins. Thus, the DNA56866-1342 clone doesencode a secreted factor. As far as is known, the DNA56866-1342 sequenceencodes a novel factor designated herein as PRO830; using the WU-BLAST-2sequence alignment computer program, no significant sequence identitiesto any known proteins were revealed.

43. Full-Length PRO1115 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1115. In particular, cDNA encoding a PRO1115 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

As far as is known, the DNA56868-1478 sequence encodes a noveltransmembrane protein designated herein as PRO1115. Although, usingWU-BLAST-2 sequence alignment computer programs, some sequenceidentities to known proteins were revealed. 44. Full-Length PRO1277Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1277. In particular, cDNA encoding a PRO1277 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

Using WU-BLAST-2 sequence alignment computer programs, it has been foundthat a full-length native sequence PRO1277 (shown in FIG. 113 and SEQ IDNO:179) has certain amino acid sequence identity with Coch-5B2 protein(designated “AF012252_(—)1” in the Dayhoff database). Accordingly, it ispresently believed that PRO1277 disclosed in the present application isa newly identified member of the Coch-5B2 protein family and may possessthe same activities and properties as Coch-5B2.

45. Full-Length PRO1135 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1135. In particular, Applicants have identified and isolated cDNAencoding a PRO1135 polypeptide, as disclosed in further detail in theExamples below. Using BLAST and FastA sequence alignment computerprograms, Applicants found that the PRO1135 polypeptide has significantsimilarity to the alpha 1,2-mannosidase protein. Accordingly, it ispresently believed that PRO1135 polypeptide disclosed in the presentapplication is a newly identified member of the mannosidase enzymefamily and possesses activity typical of that family of proteins.

46. Full-Length PRO1114 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1114 interferon receptor. In particular, cDNA encoding a PRO1114interferon receptor polypeptide has been identified and isolated, asdisclosed in further detail in the Examples below.

Using the WU-BLAST-2 sequence alignment computer program, it has beenfound that a full-length native sequence PRO1114 interferon receptorpolypeptide (shown in FIG. 117 and SEQ ID NO:183) has sequence identitywith the other known interferon receptors. Accordingly, it is presentlybelieved that PRO1114 interferon receptor possesses activity typical ofother interferon receptors.

47. Full-Length PRO828 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO828. In particular, Applicants have identified and isolated cDNAencoding a PRO828 polypeptide, as disclosed in further detail in theExamples below. Using BLAST and FastA sequence alignment computerprograms, Applicants found that the PRO828 polypeptide has sequenceidentity with glutathione peroxidases. Accordingly, it is presentlybelieved that PRO828 polypeptide disclosed in the present application isa newly identified member of the glutathione peroxidase family andpossesses peroxidase activity and other properties typical ofglutathione peroxidases.

48. Full-Length PRO1009 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1009. In particular, cDNA encoding a PRO1009 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

Using WU-BLAST-2 sequence alignment computer programs, it has been foundthat a full-length native sequence PRO1009 (shown in FIG. 122 and SEQ IDNO:194) has certain amino acid sequence identity with long-chainacyl-CoA synthetase homolog designated “F69893”. Accordingly, it ispresently believed that PRO1009 disclosed in the present application isa newly identified member of the long-chain acyl-CoA synthetase familyand may possess activity related to this family.

49. Full-Length PRO1007 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1007. In particular, Applicants have identified and isolated cDNAencoding a PRO1007 polypeptide, as disclosed in further detail in theExamples below. Using BLAST and FastA sequence alignment computerprograms, Applicants found that various portions of the PRO1007polypeptide have sequence identity with MAGPIAP. Accordingly, it ispresently believed that PRO1007 polypeptide disclosed in the presentapplication is a newly identified member of the MAGPIAP family and isassociated with metastasis and/or cell signaling and/or cellreplication.

50. Full-Length PRO1056 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1056. In particular, cDNA encoding a PRO1056 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

Using the WU-BLAST-2 sequence alignment computer program, it has beenfound that a full-length native sequence PRO1056 (shown in FIG. 127 andSEQ ID NO:199) has amino acid sequence identity with a chloride channelprotein. Accordingly, it is presently believed that PRO1056 disclosed inthe present application is a newly identified chloride channel proteinhomolog.

51. Full-Length PRO826 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO826. In particular, cDNA encoding a PRO826 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

The DNA57694-1341 clone was isolated from a human fetal heart libraryusing a trapping technique which selects for nucleotide sequencesencoding secreted proteins. Thus, the DNA57694-1341 clone does encode asecreted factor. As far as is known, the DNA57694-1341 sequence encodesa novel factor designated herein as PRO826; using the WU-BLAST-2sequence alignment computer program, no significant sequence identitiesto any known proteins were revealed.

52. Full-Length PRO819 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO819. In particular, cDNA encoding a PRO819 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

The DNA57695-1340 clone was isolated from a human fetal liver spleenlibrary using a trapping technique which selects for nucleotidesequences encoding secreted proteins. Thus, the DNA57695-1340 clone doesencode a secreted factor. As far as is known, the DNA57695-1340 sequenceencodes a novel factor designated herein as PRO819; using the WU-BLAST-2sequence alignment computer program, no significant sequence identitiesto any known proteins were revealed.

53. Full-Length PRO1006 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1006. In particular, Applicants have identified and isolated cDNAencoding a PRO1006 polypeptide, as disclosed in further detail in theExamples below. The PRO1006-encoding clone was isolated from a humanuterus library. To Applicants present knowledge, the DNA57699-1412nucleotide sequence encodes a novel factor; using BLAST and FastAsequence alignment computer programs, some sequence identity with aputative tyrosine protein kinase was revealed.

54. Full-Length PRO1112 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1112. In particular, Applicants have identified cDNA encoding aPRO1112 polypeptide, as disclosed in further detail in Example 1 below.To Applicants present knowledge, the DNA57702-1476 nucleotide sequenceencodes a novel factor, although using BLAST and FastA sequencealignment computer programs some sequence identity with other knownproteins was found.

55. Full-Length PRO1074 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1074. In particular, Applicants have identified and isolated cDNAencoding a PRO1074 polypeptide, as disclosed in further detail in theExamples below. Using BLAST and FastA sequence alignment computerprograms, Applicants found that the PRO1074 polypeptide has sequenceidentity with galactosyltransferase. Accordingly, it is presentlybelieved that PRO1074 polypeptide disclosed in the present applicationis a newly identified member of the galactosyltransferase family andpossesses galactosyltransferase activity.

56. Full-Length PRO1005 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1005. In particular, cDNA encoding a PRO1005 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

As far as is known, the DNA57708-1411 sequence encodes a novel factordesignated herein as PRO1005. However, using WU-BLAST2 sequencealignment computer programs, some sequence identities with knownproteins was revealed.

57. Full-Length PRO1073 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1073. In particular, cDNA encoding a PRO1073 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

As far as is known, the DNA57710 sequence encodes a novel secretedfactor designated herein as PRO1073. However, using WU-BLAST2 sequencealignment computer programs, some sequence identities to known proteinswere revealed.

58. Full-Length PRO1152 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1152. In particular, cDNA encoding a PRO1152 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

The DNA57711-1501 clone was isolated from a human infant brain library.As far as is known, the DNA57711-1501 sequence encodes a novel factordesignated herein as PRO1152; using the WU-BLAST-2 sequence alignmentcomputer program, no significant sequence identities to any knownproteins were revealed.

59. Full-Length PRO1136 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1136. In particular, cDNA encoding a PRO1136 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

Using the WU-BLAST2 sequence alignment computer program, it has beenfound that a full-length native sequence PRO1136 (shown in FIG. 147 andSEQ ID NO:219) has amino acid sequence identity with PDZdomain-containing proteins. Accordingly, it is presently believed thatPRO1136 disclosed in the present application is a newly identifiedmember of the PDZ domain-containing protein family and may possessactivity typical of that family.

60. Full-Length PRO813 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO813. In particular, Applicants have identified and isolated cDNAencoding a PRO813 polypeptide, as disclosed in further detail in theExamples below. Using BLAST and FastA sequence alignment computerprograms, Applicants found that the PRO813 polypeptide has significantsimilarity to the pulmonary surfactant-associated protein C.Accordingly, it is presently believed that PRO813 polypeptide disclosedin the present application is a newly identified pulmonarysurfactant-associated protein C homolog.

61. Full-Length PRO809 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO809. In particular, Applicants have identified and isolated cDNAencoding a PRO809 polypeptide, as disclosed in further detail in theExamples below. To Applicants present knowledge, the DNA57836-1338nucleotide sequence encodes a novel factor.

62. Full-Length PRO791 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO791. In particular, Applicants have identified and isolated cDNAencoding a PRO791 polypeptide, as disclosed in further detail in theExamples below. To Applicants present knowledge, the DNA57838-1337nucleotide sequence encodes a novel factor; however, using BLAST andFastA sequence alignment computer programs, there does appear to be somesequence identity with MHC-1 antigens, indicating that PRO791 may berelated thereto in structure and function.

63. Full-Length PRO1004 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1004. In particular, cDNA encoding a PRO1004 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

As far as is known, the DNA57844-1410 sequence encodes a novel factordesignated herein as PRO1004. However, using WU-BLAST2 sequencealignment computer programs, some sequence identities with knownproteins were revealed.

64. Full-Length PRO1111 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1111. In particular, cDNA encoding a PRO1111 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

Using WU-BLAST2 sequence alignment computer programs, it has been foundthat a full-length native sequence PRO1111 (shown in FIG. 157 and SEQ IDNO:229) has certain amino acid sequence identity with LIG. Accordingly,it is presently believed that PRO1111 disclosed in the presentapplication is a newly identified member of this glycoprotein family.

65. Full-Length PRO1344 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1344. In particular, cDNA encoding a PRO1344 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

Using the WU-BLAST2 sequence alignment computer program, it has beenfound that a full-length native sequence PRO1344 (shown in FIG. 159 andSEQ ID NO:231) has certain amino acid sequence identity with the factorC protein of Carcinoscorpius rotundicauda. Accordingly, it is presentlybelieved that PRO1344 disclosed in the present application is a newlyidentified factor C protein and may possess activity typical of thatprotein.

66. Full-Length PRO1109 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1109. In particular, cDNA encoding a PRO1109 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

Using the WU-BLAST2 sequence alignment computer program, it has beenfound that a full-length native sequence PRO1109 (shown in FIG. 161 andSEQ ID NO:236) has certain amino acid sequence identity with the humanUDP-Gal:GlcNAc galactosyltransferase protein. Accordingly, it ispresently believed that PRO1109 disclosed in the present application isa newly identified β-galactosyltransferase enzyme and has activitytypical of those enzymes.

67. Full-Length PRO1383 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1383. In particular, cDNA encoding a PRO1383 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

Using the WU-BLAST2 sequence alignment computer program, it has beenfound that a full-length native sequence PRO1383 (shown in FIG. 163 andSEQ ID NO:241) has certain amino acid sequence identity with theputative human transmembrane protein nmb precursor (NMB_HUMAN).Accordingly, it is presently believed that PRO1383 disclosed in thepresent application is a newly identified nmb homolog.

68. Full-Length PRO1003 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1003. In particular, Applicants have identified and isolated cDNAencoding a PRO1003 polypeptide, as disclosed in further detail in theExamples below. The PRO1003-encoding clone was isolated from a humanbreast tumor tissue library. The PRO1003-encoding clone was isolatedusing a trapping technique which selects for nucleotide sequencesencoding secreted proteins. Thus, the PRO1003-encoding clone may encodea secreted factor. To Applicants present knowledge, the UNQ487(DNA58846-1409) nucleotide sequence encodes a novel factor; using BLASTand FastA sequence alignment computer programs, no sequence identitiesto any known proteins were revealed.

69. Full-Length PRO1108 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1108. In particular, Applicants have identified and isolated cDNAencoding a PRO1108 polypeptide, as disclosed in further detail in theExamples below. Using BLAST and FastA sequence alignment computerprograms, Applicants found that the PRO1108 polypeptide has significantsimilarity to the LPAAT protein. Accordingly, it is presently believedthat PRO1108 polypeptide disclosed in the present application is a newlyidentified LPAAT homolog.

70. Full-Length PRO1137 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1137. In particular, Applicants have identified and isolated cDNAencoding a PRO1137 polypeptide, as disclosed in further detail in theExamples below. Using BLAST and FastA sequence alignment computerprograms, Applicants found that the PRO1137 polypeptide has sequenceidentity with ribosyltransferases. Accordingly, it is presently believedthat PRO1137 polypeptide disclosed in the present application is a newlyidentified member of the ribosyltransferase family and possessesribosyltransferase activity.

71. Full-Length PRO1138 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1138. In particular, Applicants have identified and isolated cDNAencoding a PRO1138 polypeptide, as disclosed in further detail in theExamples below. Using BLAST and FastA sequence alignment computerprograms, Applicants found that the PRO1138 polypeptide has sequenceidentity with CD84 leukocyte antigen. Accordingly, it is presentlybelieved that PRO1138 polypeptide disclosed in the present applicationis a newly identified member of the Ig superfamily and has activitytypical of other members of the Ig superfamily.

72. Full-Length PRO1054 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1054. In particular, cDNA encoding a PRO1054 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

Using the WU-BLAST2 sequence alignment computer program, it has beenfound that a full-length native sequence PRO1054 (shown in FIG. 174 andSEQ ID NO:256) has amino acid sequence identity with one or more of themajor urinary proteins. Accordingly, it is presently believed thatPRO1054 disclosed in the present application is a newly identifiedmember of the MUP family and may possess activity typical of thatfamily.

73. Full-Length PRO994 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO994. In particular, cDNA encoding a PRO994 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

Using the WU-BLAST2 sequence alignment computer program, it has beenfound that a full-length native sequence PRO994 (shown in FIG. 176 andSEQ ID NO:258) has amino acid sequence identity with thetumor-associated antigen L6. Accordingly, it is presently believed thatPRO994 disclosed in the present application is a newly identified L6antigen homolog.

74. Full-Length PRO812 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO812. In particular, cDNA encoding a PRO812 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

Using the WU-BLAST2 sequence alignment computer program, it has beenfound that a full-length native sequence PRO812 (shown in FIG. 178 andSEQ ID NO:260) has amino acid sequence identity with the prostaticsteroid-binding c1 protein. Accordingly, it is presently believed thatPRO812 disclosed in the present application is a newly identifiedprostatic steroid-binding c1 protein homolog.

75. Full-Length PRO1069 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1069. In particular, Applicants have identified and isolated cDNAencoding a PRO1069 polypeptide, as disclosed in further detail in theExamples below. Using BLAST and FastA sequence alignment computerprograms, it was found that the PRO1069 polypeptide has sequenceidentity with CHIF. Accordingly, it is presently believed that PRO1069polypeptide disclosed in the present application is a newly identifiedCHIF polypeptide and is involved in ion conductance or regulation of ionconductance.

76. Full-Length PRO1129 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1129. In particular, Applicants have identified and isolated cDNAencoding a PRO1129 polypeptide, as disclosed in further detail in theExamples below. Using BLAST and FastA sequence alignment computerprograms, Applicants found that the PRO1129 polypeptide has significantsimilarity to the cytochrome P-450 family of proteins. Accordingly, itis presently believed that PRO1129 polypeptide disclosed in the presentapplication is a newly identified member of the cytochrome P-450 familyand possesses activity typical of that family.

77. Full-Length PRO1068 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1068. In particular, cDNA encoding a PRO1068 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

Using WU-BLAST2 sequence alignment computer programs, it has been foundthat a full-length native sequence PRO1068 has amino acid sequenceidentity with urotensin. Accordingly, it is presently believed thatPRO1068 disclosed in the present application is a newly identifiedmember of the urotensin family and may possess activity typical of theurotensin family.

78. Full-Length PRO1066 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1066. In particular, Applicants have identified and isolated cDNAencoding a PRO1066 polypeptide, as disclosed in further detail in theExamples below. The PRO1066-encoding clone was isolated from a humanpancreatic tumor tissue library using a trapping technique which selectsfor nucleotide sequences encoding secreted proteins. Thus, thePRO1066-encoding clone may encode a secreted factor. To Applicantspresent knowledge, the DNA59215-1425 nucleotide sequence encodes a novelfactor; using BLAST and FastA sequence alignment computer programs, nosequence identities to any known proteins were revealed.

79. Full-Length PRO1184 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1184. In particular, Applicants have identified cDNA encoding aPRO1184 polypeptide, as disclosed in further detail in the Examplesbelow. To Applicants present knowledge, the DNA59220-1514 nucleotidesequence encodes a novel secreted factor.

80. Full-Length PRO1360 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1360. In particular, cDNA encoding a PRO1360 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

As far as is known, the DNA59488-1603 sequence encodes a novel factordesignated herein as PRO1360; using WU-BLAST2 sequence alignmentcomputer programs, no significant sequence identities to any knownproteins were revealed. Some sequence identities were revealed, asindicated below in the examples.

81. Full-Length PRO1029 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1029. In particular, cDNA encoding a PRO1029 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

The DNA59493-1420 clone was isolated from a human fetal liver spleenlibrary using a trapping technique which selects for nucleotidesequences encoding secreted proteins. Thus, the DNA59493-1420 clone doesencode a secreted factor. As far as is known, the DNA59493-1420 sequenceencodes a novel factor designated herein as PRO1029; using the WU-BLAST2sequence alignment computer program, no sequence identities to any knownproteins were revealed.

82. Full-Length PRO1139 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1139. In particular, Applicants have identified and isolated cDNAsencoding PRO1139, as disclosed in further detail in the Examples below.Using BLAST and FastA sequence alignment computer programs, Applicantsfound that the human PRO1139 protein originally identified exhibits asignificant sequence homology to the a OB receptor associated proteinHSOBRGRP_(—)1, described by Bailleul et al., Nucleic Acids Res. 25,2752–2758 (1997) (EMBL Accession No: Y12670).

83. Full-Length PRO1309 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1309. In particular, cDNA encoding a PRO1309 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

Using the WU-BLAST2 sequence alignment computer program, it has beenfound that a full-length native sequence PRO1309 (shown in FIG. 196 andSEQ ID NO:278) has certain amino acid sequence identity with a proteindesignated KIAA0416, given the Dayhoff designation AB007876_(—)1.Moreover, PRO1309 has leucine rich repeats, accordingly, it is presentlybelieved that PRO1309 disclosed in the present application is a newlyidentified member of the leucine rich protein family and may be involvedin protein interactions.

84. Full-Length PRO1028 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1028. In particular, Applicants have identified and isolated cDNAencoding a PRO1028 polypeptide, as disclosed in further detail in theExamples below. To Applicants present knowledge, the DNA59603-1419nucleotide sequence encodes a novel factor. BLAST and FastA sequencealignment computer programs showed some sequence identity with proteinssuch as those designated “A53050” and EMU39529_(—)1”.

85. Full-Length PRO1027 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1027. In particular, Applicants have identified and isolated cDNAencoding a PRO1027 polypeptide, as disclosed in further detail in theExamples below. The PRO1027-encoding clone was identified in a humanuterine cervical tissue library. To Applicants present knowledge, theDNA59605-1418 nucleotide sequence encodes a novel factor.

86. Full-Length PRO1107 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1107. In particular, Applicants have identified and isolated cDNAencoding a PRO1107 polypeptide, as disclosed in further detail in theExamples below. Using BLAST and FastA sequence alignment computerprograms, Applicants found that the PRO1107 polypeptide has somesimilarity to the PC-1 protein, human insulin receptor tyrosine kinaseinhibitor, an alkaline phosphodiesterase, and autotaxin. Accordingly, itis presently believed that PRO1107 polypeptide disclosed in the presentapplication is a newly identified member of the phosphodiesterasefamily.

87. Full-Length PRO1140 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding novel multi-span transmembrane polypeptides referredto in the present application as PRO1140. In particular, Applicants haveidentified and isolated cDNA encoding a PRO1140 polypeptide, asdisclosed in further detail in the Examples below. Using BLAST and FastAsequence alignment computer programs, some sequence identity with knownproteins was found.

88. Full-Length PRO1106 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1106. In particular, Applicants have identified and isolated cDNAencoding a PRO1106 polypeptide, as disclosed in further detail in theExamples below. Using BLAST and FastA sequence alignment computerprograms, Applicants found that the PRO1106 polypeptide has significantsimilarity to the peroxisomal calcium-dependent solute carrier.Accordingly, it is presently believed that PRO1106 polypeptide disclosedin the present application is a newly identified member of themitochondrial carrier superfamily and possesses transporter activitytypical of this family.

89. Full-Length PRO1291 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1291. In particular, cDNA encoding a PRO1291 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

Using the WU-BLAST2 sequence alignment computer program, it has beenfound that a full-length native sequence PRO1291 (shown in FIG. 208 andSEQ ID NO:291) has certain amino acid sequence identity with thebutyrophilin protein. Accordingly, it is presently believed that PRO1291disclosed in the present application is a newly identified butyrophilinhomolog and may possess activity typical of that protein.

90. Full-Length PRO1105 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1105. In particular, Applicants have identified cDNA encoding aPRO1105 polypeptide, as disclosed in further detail in the Examplesbelow. To Applicants present knowledge, the DNA59612-1466 nucleotidesequence encodes a novel factor. There is, however, some sequenceidentity with a peroxydase precursor designated in a Dayhoff database as“ATTS1623_(—)1”.

91. Full-Length PRO511 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO511. In particular, Applicants have identified and isolated cDNAencoding a PRO511 polypeptide, as disclosed in further detail in theExamples below. The PRO511-encoding clone was isolated from a humancolon tissue library. To Applicants present knowledge, the DNA59613-1417nucleotide sequence encodes a novel factor; using BLAST and FastAsequence alignment computer programs, sequence identities with RoBo-1,phospholipase inhibitors and a protein designated as “SSC20F10_(—)1”were revealed, indicated that PRO511 may be related to one or more ofthese proteins.

92. Full-Length PRO1104 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1104. In particular, Applicants have identified and isolated cDNAencoding a PRO1104 polypeptide, as disclosed in further detail in theExamples below. To Applicants present knowledge, the DNA59616-1465nucleotide sequence encodes a novel factor; using BLAST and FastAsequence alignment computer programs, some sequence identity appearedwith proteins designated as “AB002107_(—)1”, “AF022991_(—)1” andSP96_DICDI”.

93. Full-Length PRO1100 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationsPRO1100. In particular, Applicants have identified cDNA encoding aPRO1100 polypeptide, as disclosed in further detail in the Examplesbelow. To Applicants present knowledge, the DNA59619-1464 nucleotidesequence encodes a novel factor; using BLAST and FastA sequencealignment computer programs, only some sequence identity with knownproteins was revealed. There is some sequence identity with the yeasthypothetical 42.5 KD protein in TSM1-ARE1 intergenic region (ACCESSIONNO: 140496), designated “YSCT4_YEAST”.

94. Full-Length PRO836 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO836. In particular, Applicants have identified and isolated cDNAencoding a PRO836 polypeptide, as disclosed in further detail in theExamples below. To Applicants present knowledge, the DNA59620-1463nucleotide sequence encodes a novel factor. Using BLAST and FastAsequence alignment computer programs, there appears to be some sequenceidentity with SLS1.

95. Full-Length PRO1141 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1141. In particular, cDNA encoding a PRO1141 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

The DNA59625-1498 clone was isolated from a human ileum tissue library.As far as is known, the DNA59625-1498 sequence encodes a novel factordesignated herein as PRO1141; using the WU-BLAST2 sequence alignmentcomputer program, no sequence identities to any known proteins wererevealed.

96. Full-Length PRO1132 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1132. In particular, cDNA encoding a PRO1132 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

Using WU-BLAST2 sequence alignment computer program, it has been foundthat a full-length native sequence PRO1132 (shown in FIG. 226 and SEQ IDNO:309) has certain amino acid sequence identity with enamel matrixserine proteinase 1 and neuropsin. Accordingly, it is presently believedthat PRO1132 disclosed in the present application is a newly identifiedmember of the serine protease family and may possess protease activitytypical of this family.

97. Full-Length PRO1346 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas NL7 (UNQ701). In particular, cDNA encoding an NL7 polypeptide hasbeen identified and isolated, as disclosed in further detail in theExamples below.

As disclosed in the Examples below, a clone DNA59776-1600 has beendeposited with ATCC. The actual nucleotide sequence of the clone can bereadily determined by the skilled artisan by sequencing of the depositedclone using routine methods in the art. The predicted amino acidsequence can be determined from the nucleotide sequence using routineskill. For the NL7 (PRO1346) herein, Applicants have identified what isbelieved to be the reading frame best identifiable with the sequenceinformation available at the time of filing.

Using WU-BLAST2 sequence alignment computer programs, it has been foundthat a full-length native sequence NL7 (shown in FIG. 228 and SEQ IDNO:314) has certain amino acid sequence identity withmicrofibril-associated glycoprotein 4 (MFA4_HUMAN); ficolin-A—Musmusculus (AB007813_(—)1); human lectin P35 (D63155S6_(—)1); ficolinB—Mus musculus (AFO063217_(—)1); human tenascin-R (restriction)(HS518E13_(—)1); the long form of a rat janusin precursor (A45445);fibrinogen-related protein HFREP-1 precursor (JNO596); a human Tenascinprecursor (TENA HUMAN); human CDT6 (HSY16132_(—)1); andangiopoietin-1—Mus musculus (MMU83509_(—)1). It is presently believedthat NL7 disclosed in the present application is a novel TIE ligandhomologue, and may play a role in angiogenesis and/or vascularmaintenance and/pr wound healing and/or inflammation and/or tumordevelopment and/or growth.

98. Full-Length PRO1131 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1131. In particular, cDNA encoding a PRO1131 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

Using WU-BLAST2 sequence alignment computer programs, it has been foundthat a full-length native sequence PRO1131 (shown in FIG. 230 and SEQ IDNO:319) has certain amino acid sequence identity with a lectin-likeoxidized LDL receptor. Accordingly, it is presently believed thatPRO1131 disclosed in the present application may have at least onemechanism similar to those of the LDL receptors.

99. Full-Length PRO1281 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1281. In particular, cDNA encoding a PRO1281 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

The DNA59820-1549 clone was isolated from a human fetal liver libraryusing a trapping technique which selects for nucleotide sequencesencoding secreted proteins. Thus, as far as is known, the DNA59820-1549sequence encodes a novel factor designated herein as PRO1281. UsingWU-BLAST2 sequence alignment computer programs, some sequence identitiesto known proteins was found, but determined not to be significant.

100. Full-Length PRO1064 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1064. In particular, cDNA encoding a PRO1064 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

The DNA59827-1426 clone was isolated from a human fetal kidney library.As far as is known, the DNA59827-1426 sequence encodes a novel factordesignated herein as PRO1064; using the WU-BLAST2 sequence alignmentcomputer program, no significant sequence identities to any knownproteins were revealed.

101. Full-Length PRO1379 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1379. In particular, cDNA encoding a PRO1379 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

The DNA59828 clone was isolated from a human fetal kidney library. Asfar as is known, the PRO1379 polypeptide encoded thereby is a novelsecreted factor. Using WU-BLAST2 sequence alignment computer programs,sequence identity was found between PRO1379 and a hypothetical yeastprotein “YHY8_YEAST” (Dayhoff database; version 35.45 SwissProt 35),particularly at the C-terminal ends. Sequence homologies with otherknown proteins were revealed, but determined not to be significant.

102. Full-Length PRO844 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO844. In particular, Applicants have identified and isolated cDNAencoding a PRO844 polypeptide, as disclosed in further detail in theExamples below. Using BLAST and FastA sequence alignment computerprograms, Applicants found that the PRO844 polypeptide has sequenceidentity with serine protease inhibitors. Accordingly, it is presentlybelieved that PRO844 polypeptide disclosed in the present application isa newly identified serine protease inhibitor and is capable ofinhibiting serine proteases.

103. Full-Length PRO848 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO848. In particular, Applicants have identified and isolated cDNAencoding a PRO848 polypeptide, as disclosed in further detail in theExamples below. Using BLAST and FastA sequence alignment computerprograms, Applicants found that the PRO848 polypeptide has sequenceidentity with sialyltransferases. Accordingly, it is presently believedthat PRO848 polypeptide disclosed in the present application is a newlyidentified member of the sialyltransferase family and possessessialylation capabilities as typical of this family.

104. Full-Length PRO1097 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1097. In particular, Applicants have identified and isolated cDNAencoding a PRO1097 polypeptide, as disclosed in further detail in theExamples below. To Applicants present knowledge, the DNA59841-1460nucleotide sequence encodes a novel factor. Using BLAST and FastAsequence alignment computer programs, some sequence identity withproteins designated as “CELK05G3_(—)3”, “CRU26344_(—)1”,“SPBC16C6_(—)8”, “P_W13844” and “AF013403” was revealed.

105. Full-Length PRO1153 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1153. In particular, cDNA encoding a PRO1153 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

Using WU-BLAST2 sequence alignment computer programs, it has been foundthat a full-length native sequence PRO1153 (shown in FIG. 246 and SEQ IDNO:351) has certain amino acid sequence identity with HPBRII-7 proteinsubmitted to the EMBL Data Library June 1992. Accordingly, it ispresently believed that PRO1153 disclosed in the present application maybe related to HPBRII-7.

106. Full-Length PRO1154 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1154. In particular, cDNA encoding a PRO1154 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

Using WU-BLAST2 sequence alignment computer programs, it has been foundthat a full-length native sequence PRO1154 (shown in FIG. 248 and SEQ IDNO:353) aligns with a KIAA0525 protein, designated AB011097. PRO1154 hasa novel N-terminus of 73 amino acids. Accordingly, PRO1154 is believedto be novel. PRO1154 also has significant sequence identity withaminopeptidase N, insulin-regulated membrane aminopeptidase,throtropin-releasing hormone degrading enzyme and placental leucineaminopeptidase. Therefore, PRO1154 is believed to be a novelaminopeptidase, or peptide which degrades peptides.

107. Full-Length PRO1181 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1181. In particular, cDNA encoding a PRO1181 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

The DNA59847-1511 clone was isolated from a human prostate tissuelibrary using a trapping technique which selects for nucleotidesequences encoding secreted proteins. Thus, the DNA59847-1511 clone doesencode a secreted factor. As far as is known, the DNA59847-1511 sequenceencodes a novel factor designated herein as PRO1181; using the WU-BLAST2sequence alignment computer program, no significant sequence identitiesto any known proteins were revealed.

108. Full-Length PRO1182 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1182. In particular, cDNA encoding a PRO1182 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

Using the WU-BLAST2 sequence alignment computer program, it has beenfound that a full-length native sequence PRO1182 (shown in FIG. 252 andSEQ ID NO:357) has amino acid sequence identity with the conglutininprotein. Accordingly, it is presently believed that PRO1182disclosed inthe present application is a newly identified conglutinin homolog.

109. Full-Length PRO1155 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1155. In particular, cDNA encoding a PRO1155 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

Using WU-BLAST2 sequence alignment computer programs, it has been foundthat a full-length native sequence PRO1155 (shown in FIG. 254 and SEQ IDNO:359) has certain amino acid sequence identity with neurokinin B.Accordingly, it is presently believed that PRO1155 disclosed in thepresent application is a newly identified member of the tachykininfamily.

110. Full-Length PRO1156 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1156. In particular, cDNA encoding a PRO1156 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

The DNA59853-1505 clone was isolated from an adult human heart libraryusing a trapping technique which selects for nucleotide sequencesencoding secreted proteins. Thus, the DNA59853-1505 clone may encode asecreted factor. As far as is known, the DNA59853-1505 sequence encodesa novel factor designated herein as PRO1156. However, using WU-BLAST2sequence alignment computer programs, some sequence identity with knownproteins were revealed.

111. Full-Length PRO1098 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1098. In particular, Applicants have identified cDNA encoding aPRO1098 polypeptide, as disclosed in further detail in the Examplesbelow. The PRO1098-encoding clone was isolated from a human lung tissuelibrary. To Applicants present knowledge, the DNA59854-1459 nucleotidesequence encodes a novel factor; using BLAST and FastA sequencealignment computer programs, no significant sequence identities to anyknown proteins were revealed. Some sequence identity appeared withproteins such as the “Env” polyprotein and a methyltransferase.

112. Full-Length PRO1127 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1127. In particular, cDNA encoding a PRO1127 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

The DNA60283-1484 clone encodes a secreted factor. As far as is known,the DNA60283-1484 sequence encodes a novel factor designated herein asPRO1127; using WU-BLAST2 sequence alignment computer programs, minimalsequence identities to any known proteins were revealed.

113. Full-Length PRO1126 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1126. In particular, cDNA encoding a PRO1126 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

Using the WU-BLAST2 sequence alignment computer program, it has beenfound that a full-length native sequence PRO1126 (shown in FIG. 262 andSEQ ID NO:367) has certain amino acid sequence identity with theolfactomedin protein. Accordingly, it is presently believed that PRO1126disclosed in the present application is a newly identified olfactomedinhomolog and may possess activity typical of that protein.

114. Full-Length PRO1125 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1125. In particular, cDNA encoding a PRO1125 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

Using WU-BLAST2 sequence alignment computer programs, it has been foundthat a full-length native sequence PRO1125 (shown in FIG. 264 and SEQ IDNO:369) has certain amino acid sequence identity with transcriptionalrepressor rco-1. Accordingly, it is presently believed that PRO1125disclosed in the present application is a newly identified member of theWD superfamily.

115. Full-Length PRO1186 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1186. In particular, cDNA encoding a PRO1186 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

Using WU-BLAST2 sequence alignment computer programs, it has been foundthat a full-length native sequence PRO1186 (shown in FIG. 266 and SEQ IDNO:371) has amino acid sequence identity with venom protein A fromDendroaspis polylepsis polylepsis venom. Accordingly, it is presentlybelieved that PRO1186 disclosed in the present application is a newlyidentified member of venom protein A and may share a related mechanism.

116. Full-Length PRO1198 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1198. In particular, cDNA encoding a PRO1198 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

As far as is known, the DNA60622-1525 sequence encodes a novel factordesignated herein as PRO1198. However, using WU-BLAST2 sequencealignment computer programs, some sequence identity with known proteinswas found.

117. Full-Length PRO1158 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1158. In particular, cDNA encoding a PRO1158 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

The DNA60625-1507 clone was isolated from a human lung tumor tissuelibrary. As far as is known, the DNA60625-1507 sequence encodes a novelfactor designated herein as PRO1158. However, using WU-BLAST2 sequencealignment computer programs, some sequence identities with knownproteins were shown.

118. Full-Length PRO1159 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1159. In particular, cDNA encoding a PRO1159 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

The DNA60627-1508 clone was isolated from a human peripheral bloodgranulocyte tissue library using a trapping technique which selects fornucleotide sequences encoding secreted proteins. Thus, the DNA60627-1508clone does encode a secreted factor. As far as is known, theDNA60627-1508 sequence encodes a novel factor designated herein asPRO1159; using the WU-BLAST2 sequence alignment computer program, nosequence identities to any known proteins were revealed.

119. Full-Length PRO1124 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1124. In particular, cDNA encoding a PRO1124 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

Using WU-BLAST2 sequence alignment computer programs, it has been foundthat a full-length native sequence PRO1124 (shown in FIG. 274 and SEQ IDNO:377) has amino acid sequence identity with an epithelial chloridechannel protein from bos taurus. PRO1124 also has sequence identity withECAM-1. Accordingly, it is presently believed that PRO1124 disclosed inthe present application is a newly identified cell membrane proteininvolved in communication of cells either through ion channels or celladhesion molecules.

120. Full-Length PRO1287 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1287. In particular, cDNA encoding a PRO1287 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

Using the WU-BLAST2 sequence alignment computer program, it has beenfound that a full-length native sequence PRO1287 (shown in FIG. 276 andSEQ ID NO:381) has amino acid sequence identity with the radical fringeprotein from Gallus gallus (GGU82088_(—)1). Accordingly, it is presentlybelieved that PRO1287 disclosed in the present application is a newlyidentified fringe protein homolog and may possess activity typical ofthe fringe protein.

121. Full-Length PRO1312 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1312. In particular, cDNA encoding a PRO1312 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

Using WU-BLAST2 sequence alignment computer programs, some sequenceidentities with known proteins were revealed, but were determined not tobe significant. Therefore, as far as is known, the DNA61873-1574sequence encodes a novel transmembrane protein designated herein asPRO1312.

122. Full-Length PRO1192 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1192. In particular, cDNA encoding a PRO1192 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

Using WU-BLAST2 sequence alignment computer programs, it has been foundthat a full-length native sequence PRO1192 (shown in FIG. 280 and SEQ IDNO:389) has amino acid sequence identity with trout P0-like glycoprotein(GEN12838 IP1). Accordingly, it is presently believed that PRO1192disclosed in the present application is a newly identified member of themyelin P0 glycoprotein family.

123. Full-Length PRO1160 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1160. In particular, cDNA encoding a PRO1160 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

The DNA62872-1509 clone was isolated from a human breast tissue libraryusing a trapping technique which selects for nucleotide sequencesencoding secreted proteins. Thus, the DNA62872-1509 clone does encode asecreted factor. As far as is known, the DNA62872-1509 sequence encodesa novel factor designated herein as PRO1160; using the WU-BLAST2sequence alignment computer program, no significant sequence identitiesto any known proteins were revealed.

124. Full-Length PRO1187 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1187. In particular, cDNA encoding a PRO1187 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

As far as is known, the DNA62876-1517 sequence encodes a novel factordesignated herein as PRO1187; using WU-BLAST2 sequence alignmentcomputer programs, no significant sequence identities to any knownproteins were revealed.

125. Full-Length PRO1185 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1185. In particular, cDNA encoding a PRO1185 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

As far as is known, the DNA62881-1515 clone encodes a novel factordesignated herein as PRO1185; using WU-BLAST2 sequence alignmentcomputer programs, no significant sequence identities to any knownproteins were revealed.

126. Full-Length PRO1345 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1345. In particular, cDNA encoding a PRO1345 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

Using the WU-BLAST2 sequence alignment computer program, it has beenfound that a full-length native sequence PRO1345 (shown in FIG. 288 andSEQ ID NO:403) has amino acid sequence identity with the C-type lectinhomolog precursor protein of bos taurus (BTU22298_(—)1). Accordingly, itis presently believed that PRO1345 disclosed in the present applicationis a newly identified member of the C-type lectin protein family and maypossess activity typical of that family or of the tetranectin protein inparticular.

127. Full-Length PRO1245 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1245. In particular, cDNA encoding a PRO1245 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

The DNA64884-1527 clone was identified using methods that selects fornucleotide sequences encoding secreted proteins. As far as is known, theDNA64884-1527 sequence encodes a novel secreted factor designated hereinas PRO1245. Using WU-BLAST2 sequence alignment computer programs, somesequence identities to known proteins were revealed; however, it wasdetermined that they were not significant.

128. Full-Length PRO1358 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1358. In particular, cDNA encoding a PRO1358 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

Using WU-BLAST2 sequence alignment computer programs, it has been foundthat a full-length native sequence PRO1358 (shown in FIG. 292 and SEQ IDNO:410) has amino acid sequence identity with RASP-1. Accordingly, it ispresently believed that PRO1358 disclosed in the present application isa newly identified member of the serpin family of serine proteaseinhibitors and may possess serine protease inhibition activity, proteincatabolism inhibitory activity and/or be associated with regeneration oftissue.

129. Full-Length PRO1195 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1195. In particular, cDNA encoding a PRO1195 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

Using WU-BLAST2 sequence alignment computer programs, it has been foundthat a full-length native sequence PRO1195 (shown in FIG. 294 and SEQ IDNO:412) has amino acid sequence identity with MMU28486_(—)1, termed aproline rich acidic protein from Mus musculus, locus MMU28486,Accession: U28486, database GBTRANS, submitted 06, Jun., 1995 by John W.Kasik. Accordingly, it is presently believed that PRO1195 disclosed inthe present application is a newly identified member of this proteinfamily.

130. Full-Length PRO1270 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1270. In particular, cDNA encoding a PRO1270 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

Using the WU-BLAST2 sequence alignment computer program, it has beenfound that a full-length native sequence PRO1270 (shown in FIG. 296 andSEQ ID NO:414) has amino acid sequence identity with the lectin protein(XLU86699_(—)1) of Xenopus laevis. Accordingly, it is presently believedthat PRO1270 disclosed in the present application is a newly identifiedmember of the lectin protein family and may possess activity typical ofthat family.

131. Full-Length PRO1271 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1271. In particular, cDNA encoding a PRO1271 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

As far as is known, the DNA66309-1538 sequence encodes a novel factordesignated herein as PRO1271; using WU-BLAST2 sequence alignmentcomputer programs, no significant sequence identities to any knownproteins were revealed (results further described in the examplesbelow).

132. Full-Length PRO1375 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1375. In particular, cDNA encoding a PRO1375 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

Using WU-BLAST2 sequence alignment computer programs, it has been foundthat a full-length native sequence PRO1375 (shown in FIG. 300 and SEQ IDNO:418) has amino acid sequence identity PUT2. Accordingly, it ispresently believed that PRO1375 disclosed in the present application hasat least one related mechanism of PUT2.

133. Full-Length PRO1385 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1385. In particular, cDNA encoding a PRO1385 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

The DNA68869-1610 clone was isolated from a human tissue library using atrapping technique which selects for nucleotide sequences encodingsecreted proteins. Thus, the DNA68869-1610 clone does encode a secretedfactor. As far as is known, the DNA68869-1610 sequence encodes a novelfactor designated herein as PRO1385; using the WU-BLAST2 sequencealignment computer program, no significant sequence identities to anyknown proteins were revealed.

134. Full-Length PRO1387 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1387. In particular, cDNA encoding a PRO1387 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

Using the WU-BLAST2 sequence alignment computer program, it has beenfound that a full-length native sequence PRO1387 (shown in FIG. 304 andSEQ ID NO:422) has amino acid sequence identity with the myelin p0protein protein precursor (MYP0_HETFR). Accordingly, it is presentlybelieved that PRO1387 disclosed in the present application is a newlyidentified member of the myelin protein family and may possess activitytypical of that family.

135. Full-Length PRO1384 Polypeptides

The present invention provides newly identified and isolated nucleotidesequences encoding polypeptides referred to in the present applicationas PRO1384. In particular, cDNA encoding a PRO1384 polypeptide has beenidentified and isolated, as disclosed in further detail in the Examplesbelow.

Using WU-BLAST2 sequence alignment computer programs, it has been foundthat a full-length native sequence PRO1384 (shown in FIG. 306 and SEQ IDNO:424) has amino acid sequence identity with NKG2-D (AF054819_(—)1;Dayhoff database, version 35.45 SwissProt 35). Accordingly, it ispresently believed that PRO1384 disclosed in the present application isa newly identified member of the NKG2 family and may possess MHCactivation/inactivation activities typical of the NKG2 family.

B. PRO Polypeptide Variants

In addition to the full-length native sequence PRO polypeptidesdescribed herein, it is contemplated that PRO variants can be prepared.PRO variants can be prepared by introducing appropriate nucleotidechanges into the PRO DNA, and/or by synthesis of the desired PROpolypeptide. Those skilled in the art will appreciate that amino acidchanges may alter post-translational processes of the PRO, such aschanging the number or position of glycosylation sites or altering themembrane anchoring characteristics.

Variations in the native full-length sequence PRO or in various domainsof the PRO described herein, can be made, for example, using any of thetechniques and guidelines for conservative and non-conservativemutations set forth, for instance, in U.S. Pat. No. 5,364,934.Variations may be a substitution, deletion or insertion of one or morecodons encoding the PRO that results in a change in the amino acidsequence of the PRO as compared with the native sequence PRO. Optionallythe variation is by substitution of at least one amino acid with anyother amino acid in one or more of the domains of the PRO. Guidance indetermining which amino acid residue may be inserted, substituted ordeleted without adversely affecting the desired activity may be found bycomparing the sequence of the PRO with that of homologous known proteinmolecules and minimizing the number of amino acid sequence changes madein regions of high homology. Amino acid substitutions can be the resultof replacing one amino acid with another amino acid having similarstructural and/or chemical properties, such as the replacement of aleucine with a serine, i.e., conservative amino acid replacements.Insertions or deletions may optionally be in the range of about 1 to 5amino acids. The variation allowed may be determined by systematicallymaking insertions, deletions or substitutions of amino acids in thesequence and testing the resulting variants for activity exhibited bythe full-length or mature native sequence.

PRO polypeptide fragments are provided herein. Such fragments may betruncated at the N-terminus or C-terminus, or may lack internalresidues, for example, when compared with a full length native protein.Certain fragments lack amino acid residues that are not essential for adesired biological activity of the PRO polypeptide.

PRO fragments may be prepared by any of a number of conventionaltechniques. Desired peptide fragments may be chemically synthesized. Analternative approach involves generating PRO fragments by enzymaticdigestion, e.g., by treating the protein with an enzyme known to cleaveproteins at sites defined by particular amino acid residues, or bydigesting the DNA with suitable restriction enzymes and isolating thedesired fragment. Yet another suitable technique involves isolating andamplifying a DNA fragment encoding a desired polypeptide fragment, bypolymerase chain reaction (PCR). Oligonucleotides that define thedesired termini of the DNA fragment are employed at the 5′ and 3′primers in the PCR. Preferably, PRO polypeptide fragments share at leastone biological and/or immunological activity with the native PROpolypeptide disclosed herein.

In particular embodiments, conservative substitutions of interest areshown in Table 6 under the heading of preferred substitutions. If suchsubstitutions result in a change in biological activity, then moresubstantial changes, denominated exemplary substitutions in Table 6, oras further described below in reference to amino acid classes, areintroduced and the products screened.

TABLE 6 Original Exemplary Preferred Residue Substitutions SubstitutionsAla (A) val; leu; ile val Arg (R) lys; gln; asn lys Asn (N) gln; his;lys; arg gln Asp (D) glu glu Cys (C) ser ser Gln (Q) asn asn Glu (E) aspasp Gly (G) pro; ala ala His (H) asn; gln; lys; arg arg Ile (I) leu;val; met; ala; phe; leu norleucine Leu (L) norleucine; ile; val; ilemet; ala; phe Lys (K) arg; gln; asn arg Met (M) leu; phe; ile leu Phe(F) leu; val; ile; ala; tyr leu Pro (P) ala ala Ser (S) thr thr Thr (T)ser ser Trp (W) tyr; phe tyr Tyr (Y) trp; phe; thr; ser phe Val (V) ile;leu; met; phe; leu ala; norleucine

Substantial modifications in function or immunological identity of thePRO polypeptide are accomplished by selecting substitutions that differsignificantly in their effect on maintaining (a) the structure of thepolypeptide backbone in the area of the substitution, for example, as asheet or helical conformation, (b) the charge or hydrophobicity of themolecule at the target site, or (c) the bulk of the side chain.Naturally occurring residues are divided into groups based on commonside-chain properties:

-   (1) hydrophobic: norleucine, met, ala, val, leu, ile;-   (2) neutral hydrophilic: cys, ser, thr;-   (3) acidic: asp, glu;-   (4) basic: asn, gln, his, lys, arg;-   (5) residues that influence chain orientation: gly, pro; and-   (6) aromatic: trp, tyr, phe.

Non-conservative substitutions will entail exchanging a member of one ofthese classes for another class. Such substituted residues also may beintroduced into the conservative substitution sites or, more preferably,into the remaining (non-conserved) sites.

The variations can be made using methods known in the art such asoligonucleotide-mediated (site-directed) mutagenesis, alanine scanning,and PCR mutagenesis. Site-directed mutagenesis [Carter et al., Nucl.Acids Res., 13:4331 (1986); Zoller et al., Nucl. Acids Res., 10:6487(1987)], cassette mutagenesis [Wells et al., Gene, 34:315 (1985)],restriction selection mutagenesis [Wells et al., Philos. Trans. R. Soc.London SerA, 317:415 (1986)] or other known techniques can be performedon the cloned DNA to produce the PRO variant DNA.

Scanning amino acid analysis can also be employed to identify one ormore amino acids along a contiguous sequence. Among the preferredscanning amino acids are relatively small, neutral amino acids. Suchamino acids include alanine, glycine, serine, and cysteine. Alanine istypically a preferred scanning amino acid among this group because iteliminates the side-chain beyond the beta-carbon and is less likely toalter the main-chain conformation of the variant [Cunningham and Wells,Science, 244: 1081–1085 (1989)]. Alanine is also typically preferredbecause it is the most common amino acid. Further, it is frequentlyfound in both buried and exposed positions [Creighton, The Proteins, (W.H. Freeman & Co., N.Y.); Chotbia, J. Mol. Biol. 150:1 (1976)]. Ifalanine substitution does not yield adequate amounts of variant, anisoteric amino acid can be used.

C. Modifications of PRO

Covalent modifications of PRO are included within the scope of thisinvention. One type of covalent modification includes reacting targetedamino acid residues of a PRO polypeptide with an organic derivatizingagent that is capable of reacting with selected side chains or the N- orC-terminal residues of the PRO. Derivatization with bifunctional agentsis useful, for instance, for crosslinking PRO to a water-insolublesupport matrix or surface for use in the method for purifying anti-PROantibodies, and vice-versa. Commonly used crosslinking agents include,e.g., 1,1-bis(diazoacetyl)-2-phenylethane, glutaraldehyde,N-hydroxysuccinimide esters, for example, esters with 4-azidosalicylicacid, homobifunctional imidoesters, including disuccinimidyl esters suchas 3,3′-dithiobis(succinimidylpropionate), bifunctional maleimides suchas bis-N-maleimido-1,8-octane and agents such asmethyl-3-[(p-azidophenyl)dithio]propioimidate.

Other modifications include deamidation of glutaminyl and asparaginylresidues to the corresponding glutamyl and aspartyl residues,respectively, hydroxylation of proline and lysine, phosphorylation ofhydroxyl groups of seryl or threonyl residues, methylation of theα-amino groups of lysine, arginine, and histidine side chains [T. E.Creighton, Proteins: Structure and Molecular Properties, W. H. Freeman &Co., San Francisco, pp. 79–86 (1983)], acetylation of the N-terminalamine, and amidation of any C-terminal carboxyl group.

Another type of covalent modification of the PRO polypeptide includedwithin the scope of this invention comprises altering the nativeglycosylation pattern of the polypeptide. “Altering the nativeglycosylation pattern” is intended for purposes herein to mean deletingone or more carbohydrate moieties found in native sequence PRO (eitherby removing the underlying glycosylation site or by deleting theglycosylation by chemical and/or enzymatic means), and/or adding one ormore glycosylation sites that are not present in the native sequencePRO. In addition, the phrase includes qualitative changes in theglycosylation of the native proteins, involving a change in the natureand proportions of the various carbohydrate moieties present.

Addition of glycosylation sites to the PRO polypeptide may beaccomplished by altering the amino acid sequence. The alteration may bemade, for example, by the addition of, or substitution by, one or moreserine or threonine residues to the native sequence PRO (for O-linkedglycosylation sites). The PRO amino acid sequence may optionally bealtered through changes at the DNA level, particularly by mutating theDNA encoding the PRO polypeptide at preselected bases such that codonsare generated that will translate into the desired amino acids.

Another means of increasing the number of carbohydrate moieties on thePRO polypeptide is by chemical or enzymatic coupling of glycosides tothe polypeptide. Such methods are described in the art, e.g., in WO87/05330 published 11, Sep. 1987, and in Aplin and Wriston, CRC Crit.Rev. Biochem., pp. 259–306 (1981).

Removal of carbohydrate moieties present on the PRO polypeptide may beaccomplished chemically or enzymatically or by mutational substitutionof codons encoding for amino acid residues that serve as targets forglycosylation. Chemical deglycosylation techniques are known in the artand described, for instance, by Hakimuddin, et al., Arch. Biochem.Biophys., 259:52 (1987) and by Edge et al., Anal. Biochem., 118:131(1981). Enzymatic cleavage of carbohydrate moieties on polypeptides canbe achieved by the use of a variety of endo- and exo-glycosidases asdescribed by Thotakura et al., Meth. Enzymol., 138:350 (1987).

Another type of covalent modification of PRO comprises linking the PROpolypeptide to one of a variety of nonproteinaceous polymers, e.g.,polyethylene glycol (PEG), polypropylene glycol, or polyoxyalkylenes, inthe manner set forth in U.S. Pat. Nos. 4,640,835; 4,496,689; 4,301,144;4,670,417; 4,791,192 or 4,179,337.

The PRO of the present invention may also be modified in a way to form achimeric molecule comprising PRO fused to another, heterologouspolypeptide or amino acid sequence.

In one embodiment, such a chimeric molecule comprises a fusion of thePRO with a tag polypeptide which provides an epitope to which ananti-tag antibody can selectively bind. The epitope tag is generallyplaced at the amino- or carboxyl-terminus of the PRO. The presence ofsuch epitope-tagged forms of the PRO can be detected using an antibodyagainst the tag polypeptide. Also, provision of the epitope tag enablesthe PRO to be readily purified by affinity purification using ananti-tag antibody or another type of affinity matrix that binds to theepitope tag. Various tag polypeptides and their respective antibodiesare well known in the art. Examples include poly-histidine (poly-his) orpoly-histidine-glycine (poly-his-gly) tags; the flu HA tag polypeptideand its antibody 12CA5 [Field et al., Mol. Cell. Biol., 8:2159–2165(1988)]; the c-myc tag and the 8F9, 3C7, 6E10, G4, B7 and 9E10antibodies thereto [Evan et al., Molecular and Cellular Biology,5:3610–3616 (1985)]; and the Herpes Simplex virus glycoprotein D (gD)tag and its antibody [Paborsky et al., Protein Engineering, 3(6):547–553(1990)]. Other tag polypeptides include the Flag-peptide [Hopp et al.,BioTechnology, 6:1204–1210 (1988)]; the KT3 epitope peptide [Martin etal., Science, 255:192–194 (1992)]; an α-tubulin epitope peptide [Skinneret al., J. Biol. Chem., 266:15163–15166 (1991)]; and the T7 gene 10protein peptide tag [Lutz-Freyermuth et al., Proc. Natl. Acad. Sci. USA,87:6393–6397 (1990)].

In an alternative embodiment, the chimeric molecule may comprise afusion of the PRO with an immunoglobulin or a particular region of animmunoglobulin. For a bivalent form of the chimeric molecule (alsoreferred to as an “immunoadhesin”), such a fusion could be to the Fcregion of an IgG molecule. The Ig fusions preferably include thesubstitution of a soluble (transmembrane domain deleted or inactivated)form of a PRO polypeptide in place of at least one variable regionwithin an Ig molecule. In a particularly preferred embodiment, theimmunoglobulin fusion includes the hinge, CH2 and CH3, or the hinge,CH1, CH2 and CH3 regions of an IgG1 molecule. For the production ofimmunoglobulin fusions see also U.S. Pat. No. 5,428,130 issued Jun. 27,1995.

D. Preparation of PRO

The description below relates primarily to production of PRO byculturing cells transformed or transfected with a vector containing PROnucleic acid. It is, of course, contemplated that alternative methods,which are well known in the art, may be employed to prepare PRO. Forinstance, the PRO sequence, or portions thereof, may be produced bydirect peptide synthesis using solid-phase techniques [see, e.g.,Stewart et al., Solid-Phase Peptide Synthesis, W. H. Freeman Co., SanFrancisco, Calif. (1969); Merrifield, J. Am. Chem. Soc., 85:2149–2154(1963)]. In vitro protein synthesis may be performed using manualtechniques or by automation. Automated synthesis may be accomplished,for instance, using an Applied Biosystems Peptide Synthesizer (FosterCity, Calif.) using manufacturer's instructions. Various portions of thePRO may be chemically synthesized separately and combined using chemicalor enzymatic methods to produce the full-length PRO.

1. Isolation of DNA Encoding PRO

DNA encoding PRO may be obtained from a cDNA library prepared fromtissue believed to possess the PRO mRNA and to express it at adetectable level. Accordingly, human PRO DNA can be convenientlyobtained from a cDNA library prepared from human tissue, such asdescribed in the Examples. The PRO-encoding gene may also be obtainedfrom a genomic library or by known synthetic procedures (e.g., automatednucleic acid synthesis).

Libraries can be screened with probes (such as antibodies to the PRO oroligonucleotides of at least about 20–80 bases) designed to identify thegene of interest or the protein encoded by it. Screening the cDNA orgenomic library with the selected probe may be conducted using standardprocedures, such as described in Sambrook et al., Molecular Cloning: ALaboratory Manual (New York: Cold Spring Harbor Laboratory Press, 1989).An alternative means to isolate the gene encoding PRO is to use PCRmethodology [Sambrook et al., supra; Dieffenbach et al., PCR Primer: ALaboratory Manual (Cold Spring Harbor Laboratory Press, 1995)].

The Examples below describe techniques for screening a cDNA library. Theoligonucleotide sequences selected as probes should be of sufficientlength and sufficiently unambiguous that false positives are minimized.The oligonucleotide is preferably labeled such that it can be detectedupon hybridization to DNA in the library being screened. Methods oflabeling are well known in the art, and include the use of radiolabelslike ³²P-labeled ATP, biotinylation or enzyme labeling. Hybridizationconditions, including moderate stringency and high stringency, areprovided in Sambrook et al., supra.

Sequences identified in such library screening methods can be comparedand aligned to other known sequences deposited and available in publicdatabases such as GenBank or other private sequence databases. Sequenceidentity (at either the amino acid or nucleotide level) within definedregions of the molecule or across the full-length sequence can bedetermined using methods known in the art and as described herein.

Nucleic acid having protein coding sequence may be obtained by screeningselected cDNA or genomic libraries using the deduced amino acid sequencedisclosed herein for the first time, and, if necessary, usingconventional primer extension procedures as described in Sambrook etal., supra, to detect precursors and processing intermediates of mRNAthat may not have been reverse-transcribed into cDNA.

2. Selection and Transformation of Host Cells

Host cells are transfected or transformed with expression or cloningvectors described herein for PRO production and cultured in conventionalnutrient media modified as appropriate for inducing promoters, selectingtransformants, or amplifying the genes encoding the desired sequences.The culture conditions, such as media, temperature, pH and the like, canbe selected by the skilled artisan without undue experimentation. Ingeneral, principles, protocols, and practical techniques for maximizingthe productivity of cell cultures can be found in Mammalian CellBiotechnology: a Practical Approach, M. Butler, ed. (IRL Press, 1991)and Sambrook et al., supra.

Methods of eukaryotic cell transfection and prokaryotic celltransformation are known to the ordinarily skilled artisan, for example,CaCl₂, CaPO₄, liposome-mediated and electroporation. Depending on thehost cell used, transformation is performed using standard techniquesappropriate to such cells. The calcium treatment employing calciumchloride, as described in Sambrook et al., supra, or electroporation isgenerally used for prokaryotes. Infection with Agrobacterium tumefaciensis used for transformation of certain plant cells, as described by Shawet al., Gene, 23:315 (1983) and WO 89/05859 published 29, Jun. 1989. Formammalian cells without such cell walls, the calcium phosphateprecipitation method of Graham and van der Eb, Virology, 52:456–457(1978) can be employed. General aspects of mammalian cell host systemtransfections have been described in U.S. Pat. No. 4,399,216.Transformations into yeast are typically carried out according to themethod of Van Solingen et al., J. Bact., 130:946 (1977) and Hsiao etal., Proc. Natl. Acad. Sci. (USA), 76:3829 (1979). However, othermethods for introducing DNA into cells, such as by nuclearmicroinjection, electroporation, bacterial protoplast fusion with intactcells, or polycations, e.g., polybrene, polyornithine, may also be used.For various techniques for transforming mammalian cells, see Keown etal., Methods in Enzymology, 185:527–537 (1990) and Mansour et al.,Nature, 336:348–352 (1988).

Suitable host cells for cloning or expressing the DNA in the vectorsherein include prokaryote, yeast, or higher eukaryote cells. Suitableprokaryotes include but are not limited to eubacteria, such asGram-negative or Gram-positive organisms, for example,Enterobacteriaceae such as E. coli. Various E. coli strains are publiclyavailable, such as E. coli K12 strain MM294 (ATCC 31,446); E. coli X1776(ATCC 31,537); E. coli strain W3110 (ATCC 27,325) and K5 772 (ATCC53,635). Other suitable prokaryotic host cells includeEnterobacteriaceae such as Escherichia, e.g., E. coli, Enterobacter,Erwinia, Klebsiella, Proteus, Salmonella, e.g., Salmonella typhimurium,Serratia, e.g., Serratia marcescans, and Shigella, as well as Bacillisuch as B. subtilis and B. licheniformis (e.g., B. licheniformis 41Pdisclosed in DD 266,710 published 12, Apr. 1989), Pseudomonas such as P.aeruginosa, and Streptomyces. These examples are illustrative ratherthan limiting. Strain W3110 is one particularly preferred host or parenthost because it is a common host strain for recombinant DNA productfermentations. Preferably, the host cell secretes minimal amounts ofproteolytic enzymes. For example, strain W3110 may be modified to effecta genetic mutation in the genes encoding proteins endogenous to thehost, with examples of such hosts including E. coli W3110 strain 1A2,which has the complete genotype tonA ; E. coli W3110 strain 9E4, whichhas the complete genotype tonA ptr3; E. coli W3110 strain 27C7 (ATCC55,244), which has the complete genotype tonA ptr3 phoA E15 (argF-lac)169 degP ompT kan^(r) ; E. coli W3110 strain 37D6, which has thecomplete genotype tonA ptr3 phoA E15 (argF-lac)169 degP ompT rbs7 ilvGkan^(r) ; E. coli W3110 strain 40B4, which is strain 37D6 with anon-kanamycin resistant degP deletion mutation; and an E. coli strainhaving mutant periplasmic protease disclosed in U.S. Pat. No. 4,946,783issued 7, Aug. 1990. Alternatively, in vitro methods of cloning, e.g.,PCR or other nucleic acid polymerase reactions, are suitable.

In addition to prokaryotes, eukaryotic microbes such as filamentousfungi or yeast are suitable cloning or expression hosts for PRO-encodingvectors. Saccharomyces cerevisiae is a commonly used lower eukaryotichost microorganism. Others include Schizosaccharomyces pombe (Beach andNurse, Nature, 290: 140 [1981]; EP 139,383 published 2, May 1985);Kluyveromyces hosts (U.S. Pat. No. 4,943,529; Fleer et al.,Bio/Technology, 9:968–975 (1991)) such as, e.g., K. lactis (MW98-8C,CBS683, CBS4574; Louvencourt et al., J. Bacteriol., 154(2):737–742[1983]), K. fragilis (ATCC 12,424), K. bulgaricus (ATCC 16,045), K.wickeramii (ATCC 24,178), K. waltii (ATCC 56,500), K. drosophilarum(ATCC 36,906; Van den Berg et al., Bio/Technology, 8:135 (1990)), K.thermotolerans, and K. marxianus; yarrowia (EP 402,226); Pichia pastoris(EP 183,070; Sreekrishna et al., J. Basic Microbiol., 28:265–278[1988]); Candida; Trichoderma reesia (EP 244,234); Neurospora crassa(Case et al., Proc. Natl. Acad. Sci. USA, 76:5259–5263 [1979]);Schwanniomyces such as Schwanniomyces occidentalis (EP 394,538 published31, Oct. 1990); and filamentous fungi such as, e.g., Neurospora,Penicillium, Tolypocladium (WO 91/00357 published 10, Jan. 1991), andAspergillus hosts such as A. nidulans (Ballance et al., Biochem.Biophys. Res. Commun., 112:284–289 [1983]; Tilburn et al., Gene,26:205–221 [1983]; Yelton et al., Proc. Natl. Acad. Sci. USA, 81:1470–1474 [1984]) and A. niger (Kelly and Hynes, EMBO J., 4:475–479[1985]). Methylotropic yeasts are suitable herein and include, but arenot limited to, yeast capable of growth on methanol selected from thegenera consisting of Hansenula, Candida, Kloeckera, Pichia,Saccharomyces, Torulopsis, and Rhodotorula. A list of specific speciesthat are exemplary of this class of yeasts may be found in C. Anthony,The Biochemistry of Methylotrophs, 269 (1982).

Suitable host cells for the expression of glycosylated PRO are derivedfrom multicellular organisms. Examples of invertebrate cells includeinsect cells such as Drosophila S2 and Spodoptera Sf9, as well as plantcells. Examples of useful mammalian host cell lines include Chinesehamster ovary (CHO) and COS cells. More specific examples include monkeykidney CVI line transformed by SV40 (COS-7, ATCC CRL 1651); humanembryonic kidney line (293 or 293 cells subcloned for growth insuspension culture, Graham et al., J. Gen Virol., 36:59 (1977)); Chinesehamster ovary cells/-DHFR (CHO, Urlaub and Chasin, Proc. Natl. Acad.Sci. USA, 77:4216 (1980)); mouse sertoli cells (TM4, Mather, Biol.Reprod., 23:243–251 (1980)); human lung cells (W138, ATCC CCL 75); humanliver cells (Hep G2, HB 8065); and mouse mammary tumor (MMT 060562, ATCCCCL51). The selection of the appropriate host cell is deemed to bewithin the skill in the art.

3. Selection and Use of a Replicable Vector

The nucleic acid (e.g., cDNA or genomic DNA) encoding PRO may beinserted into a replicable vector for cloning (amplification of the DNA)or for expression. Various vectors are publicly available. The vectormay, for example, be in the form of a plasmid, cosmid, viral particle,or phage. The appropriate nucleic acid sequence may be inserted into thevector by a variety of procedures. In general, DNA is inserted into anappropriate restriction endonuclease site(s) using techniques known inthe art. Vector components generally include, but are not limited to,one or more of a signal sequence, an origin of replication, one or moremarker genes, an enhancer element, a promoter, and a transcriptiontermination sequence. Construction of suitable vectors containing one ormore of these components employs standard ligation techniques which areknown to the skilled artisan.

The PRO may be produced recombinantly not only directly, but also as afusion polypeptide with a heterologous polypeptide, which may be asignal sequence or other polypeptide having a specific cleavage site atthe N-terminus of the mature protein or polypeptide. In general, thesignal sequence may be a component of the vector, or it may be a part ofthe PRO-encoding DNA that is inserted into the vector. The signalsequence may be a prokaryotic signal sequence selected, for example,from the group of the alkaline phosphatase, penicillinase, lpp, orheat-stable enterotoxin II leaders. For yeast secretion the signalsequence may be, e.g., the yeast invertase leader, alpha factor leader(including Saccharomyces and Kluyveromyces α-factor leaders, the latterdescribed in U.S. Pat. No. 5,010,182), or acid phosphatase leader, theC. albicans glucoamylase leader (EP 362,179 published 4, Apr. 1990), orthe signal described in WO 90/13646 published 15, Nov. 1990. Inmammalian cell expression, mammalian signal sequences may be used todirect secretion of the protein, such as signal sequences from secretedpolypeptides of the same or related species, as well as viral secretoryleaders.

Both expression and cloning vectors contain a nucleic acid sequence thatenables the vector to replicate in one or more selected host cells. Suchsequences are well known for a variety of bacteria, yeast, and viruses.The origin of replication from the plasmid pBR322 is suitable for mostGram-negative bacteria, the 2 μ plasmid origin is suitable for yeast,and various viral origins (SV40, polyoma, adenovirus, VSV or BPV) areuseful for cloning vectors in mammalian cells.

Expression and cloning vectors will typically contain a selection gene,also termed a selectable marker. Typical selection genes encode proteinsthat (a) confer resistance to antibiotics or other toxins, e.g.,ampicillin, neomycin, methotrexate, or tetracycline, (b) complementauxotrophic deficiencies, or (c) supply critical nutrients not availablefrom complex media, e.g., the gene encoding D-alanine racemase forBacilli.

An example of suitable selectable markers for mammalian cells are thosethat enable the identification of cells competent to take up thePRO-encoding nucleic acid, such as DHFR or thymidine kinase. Anappropriate host cell when wild-type DHFR is employed is the CHO cellline deficient in DHFR activity, prepared and propagated as described byUrlaub et al., Proc. Natl. Acad. Sci. USA, 77:4216 (1980). A suitableselection gene for use in yeast is the trp1 gene present in the yeastplasmid YRp7 [Stinchcomb et al., Nature, 282:39 (1979); Kingsman et al.,Gene, 7:141 (1979); Tschemper et al., Gene, 10:157 (1980)]. The trp1gene provides a selection marker for a mutant strain of yeast lackingthe ability to grow in tryptophan, for example, ATCC No. 44076 or PEP4-1[Jones, Genetics, 85:12 (1977)].

Expression and cloning vectors usually contain a promoter operablylinked to the PRO-encoding nucleic acid sequence to direct mRNAsynthesis. Promoters recognized by a variety of potential host cells arewell known. Promoters suitable for use with prokaryotic hosts includethe β-lactamase and lactose promoter systems [Chang et al., Nature,275:615 (1978); Goeddel et al., Nature, 281:544 (1979)], alkalinephosphatase, a tryptophan (trp) promoter system [Goeddel, Nucleic AcidsRes., 8:4057 (1980); EP 36,776], and hybrid promoters such as the tacpromoter [deBoer et al., Proc. Natl. Acad. Sci. USA, 80:21–25 (1983)].Promoters for use in bacterial systems also will contain aShine-Dalgarno (S.D.) sequence operably linked to the DNA encoding PRO.

Examples of suitable promoting sequences for use with yeast hostsinclude the promoters for 3-phosphoglycerate kinase [Hitzemanet al., J.Biol. Chem., 255:2073 (1980)] or other glycolytic enzymes [Hess et al.,J. Adv. Enzyme Reg., 7:149 (1968); Holland, Biochemistry, 17:4900(1978)], such as enolase, glyceraldehyde-3-phosphate dehydrogenase,hexokinase, pyruvate decarboxylase, phosphofructokinase,glucose-6-phosphate isomerase, 3-phosphoglycerate mutase, pyruvatekinase, triosephosphate isomerase, phosphoglucose isomerase, andglucokinase.

Other yeast promoters, which are inducible promoters having theadditional advantage of transcription controlled by growth conditions,are the promoter regions for alcohol dehydrogenase 2, isocytochrome C,acid phosphatase, degradative enzymes associated with nitrogenmetabolism, metallothionein, glyceraldehyde-3-phosphate dehydrogenase,and enzymes responsible for maltose and galactose utilization. Suitablevectors and promoters for use in yeast expression are further describedin EP 73,657.

PRO transcription from vectors in mammalian host cells is controlled,for example, by promoters obtained from the genomes of viruses such aspolyoma virus, fowlpox virus (UK 2,211,504 published 5, Jul. 1989),adenovirus (such as Adenovirus 2), bovine papilloma virus, avian sarcomavirus, cytomegalovirus, a retrovirus, hepatitis-B virus and Simian Virus40 (SV40), from heterologous mammalian promoters, e.g., the actinpromoter or an immunoglobulin promoter, and from heat-shock promoters,provided such promoters are compatible with the host cell systems.

Transcription of a DNA encoding the PRO by higher eukaryotes may beincreased by inserting an enhancer sequence into the vector. Enhancersare cis-acting elements of DNA, usually about from 10 to 300 bp, thatact on a promoter to increase its transcription. Many enhancer sequencesare now known from mammalian genes (globin, elastase, albumin,α-fetoprotein, and insulin). Typically, however, one will use anenhancer from a eukaryotic cell virus. Examples include the SV40enhancer on the late side of the replication origin (bp 100–270), thecytomegalovirus early promoter enhancer, the polyoma enhancer on thelate side of the replication origin, and adenovirus enhancers. Theenhancer may be spliced into the vector at a position 5′ or 3′ to thePRO coding sequence, but is preferably located at a site 5′ from thepromoter.

Expression vectors used in eukaryotic host cells (yeast, fungi, insect,plant, animal, human, or nucleated cells from other multicellularorganisms) will also contain sequences necessary for the termination oftranscription and for stabilizing the mRNA. Such sequences are commonlyavailable from the 5′ and, occasionally 3′, untranslated regions ofeukaryotic or viral DNAs or cDNAs. These regions contain nucleotidesegments transcribed as polyadenylated fragments in the untranslatedportion of the mRNA encoding PRO.

Still other methods, vectors, and host cells suitable for adaptation tothe synthesis of PRO in recombinant vertebrate cell culture aredescribed in Gething et al., Nature, 293:620–625 (1981); Mantei et al.,Nature, 281:40–46 (1979); EP 117,060; and EP 117,058.

4. Detecting Gene Amplification/Expression

Gene amplification and/or expression may be measured in a sampledirectly, for example, by conventional Southern blotting, Northernblotting to quantitate the transcription of mRNA [Thomas, Proc. Natl.Acad. Sci. USA, 77:5201–5205 (1980)], dot blotting (DNA analysis), or insitu hybridization, using an appropriately labeled probe, based on thesequences provided herein. Alternatively, antibodies may be employedthat can recognize specific duplexes, including DNA duplexes, RNAduplexes, and DNA-RNA hybrid duplexes or DNA-protein duplexes. Theantibodies in turn may be labeled and the assay may be carried out wherethe duplex is bound to a surface, so that upon the formation of duplexon the surface, the presence of antibody bound to the duplex can bedetected.

Gene expression, alternatively, may be measured by immunologicalmethods, such as immunohistochemical staining of cells or tissuesections and assay of cell culture or body fluids, to quantitatedirectly the expression of gene product. Antibodies useful forimmunohistochemical staining and/or assay of sample fluids may be eithermonoclonal or polyclonal, and may be prepared in any mammal.Conveniently, the antibodies may be prepared against a native sequencePRO polypeptide or against a synthetic peptide based on the DNAsequences provided herein or against exogenous sequence fused to PRO DNAand encoding a specific antibody epitope.

5. Purification of Polypeptide

Forms of PRO may be recovered from culture medium or from host celllysates. If membrane-bound, it can be released from the membrane using asuitable detergent solution (e.g. Triton-X 100) or by enzymaticcleavage. Cells employed in expression of PRO can be disrupted byvarious physical or chemical means, such as freeze-thaw cycling,sonication, mechanical disruption, or cell lysing agents.

It may be desired to purify PRO from recombinant cell proteins orpolypeptides. The following procedures are exemplary of suitablepurification procedures: by fractionation on an ion-exchange column;ethanol precipitation; reverse phase HPLC; chromatography on silica oron a cation-exchange resin such as DEAE; chromatofocusing; SDS-PAGE;ammonium sulfate precipitation; gel filtration using, for example,Sephadex G-75; protein A Sepharose columns to remove contaminants suchas IgG; and metal chelating columns to bind epitope-tagged forms of thePRO. Various methods of protein purification may be employed and suchmethods are known in the art and described for example in Deutscher,Methods in Enzymology, 182 (1990); Scopes, Protein Purification:Principles and Practice, Springer-Verlag, New York (1982). Thepurification step(s) selected will depend, for example, on the nature ofthe production process used and the particular PRO produced.

E. Uses for PRO

Nucleotide sequences (or their complement) encoding PRO have variousapplications in the art of molecular biology, including uses ashybridization probes, in chromosome and gene mapping and in thegeneration of anti-sense RNA and DNA. PRO nucleic acid will also beuseful for the preparation of PRO polypeptides by the recombinanttechniques described herein.

The full-length native sequence PRO gene, or portions thereof, may beused as hybridization probes for a cDNA library to isolate thefull-length PRO cDNA or to isolate still other cDNAs (for instance,those encoding naturally-occurring variants of PRO or PRO from otherspecies) which have a desired sequence identity to the native PROsequence disclosed herein. Optionally, the length of the probes will beabout 20 to about 50 bases. The hybridization probes may be derived fromat least partially novel regions of the full length native nucleotidesequence wherein those regions may be determined without undueexperimentation or from genomic sequences including promoters, enhancerelements and introns of native sequence PRO. By way of example, ascreening method will comprise isolating the coding region of the PROgene using the known DNA sequence to synthesize a selected probe ofabout 40 bases. Hybridization probes may be labeled by a variety oflabels, including radionucleotides such as ³²p or ³⁵S, or enzymaticlabels such as alkaline phosphatase coupled to the probe viaavidin/biotin coupling systems. Labeled probes having a sequencecomplementary to that of the PRO gene of the present invention can beused to screen libraries of human cDNA, genomic DNA or mRNA to determinewhich members of such libraries the probe hybridizes to. Hybridizationtechniques are described in further detail in the Examples below.

Any EST sequences disclosed in the present application may similarly beemployed as probes, using the methods disclosed herein.

Other useful fragments of the PRO nucleic acids include antisense orsense oligonucleotides comprising a singe-stranded nucleic acid sequence(either RNA or DNA) capable of binding to target PRO mRNA (sense) or PRODNA (antisense) sequences. Antisense or sense oligonucleotides,according to the present invention, comprise a fragment of the codingregion of PRO DNA. Such a fragment generally comprises at least about 14nucleotides, preferably from about 14 to 30 nucleotides. The ability toderive an antisense or a sense oligonucleotide, based upon a cDNAsequence encoding a given protein is described in, for example, Steinand Cohen (Cancer Res. 48:2659, 1988) and van der Krol et al.(BioTechnigues 6:958, 1988).

Binding of antisense or sense oligonucleotides to target nucleic acidsequences results in the formation of duplexes that block transcriptionor translation of the target sequence by one of several means, includingenhanced degradation of the duplexes, premature termination oftranscription or translation, or by other means. The antisenseoligonucleotides thus may be used to block expression of PRO proteins.Antisense or sense oligonucleotides further comprise oligonucleotideshaving modified sugar-phosphodiester backbones (or other sugar linkages,such as those described in WO 91/06629) and wherein such sugar linkagesare resistant to endogenous nucleases. Such oligonucleotides withresistant sugar linkages are stable in vivo (i.e., capable of resistingenzymatic degradation) but retain sequence specificity to be able tobind to target nucleotide sequences.

Other examples of sense or antisense oligonucleotides include thoseoligonucleotides which are covalently linked to organic moieties, suchas those described in WO 90/10048, and other moieties that increasesaffinity of the oligonucleotide for a target nucleic acid sequence, suchas poly-(L-lysine). Further still, intercalating agents, such asellipticine, and alkylating agents or metal complexes may be attached tosense or antisense oligonucleotides to modify binding specificities ofthe antisense or sense oligonucleotide for the target nucleotidesequence.

Antisense or sense oligonucleotides may be introduced into a cellcontaining the target nucleic acid sequence by any gene transfer method,including, for example, CaPO₄-mediated DNA transfection,electroporation, or by using gene transfer vectors such as Epstein-Barrvirus. In a preferred procedure, an antisense or sense oligonucleotideis inserted into a suitable retroviral vector. A cell containing thetarget nucleic acid sequence is contacted with the recombinantretroviral vector, either in vivo or ex vivo. Suitable retroviralvectors include, but are not limited to, those derived from the murineretrovirus M-MuLV, N2 (a retrovirus derived from M-MuLV), or the doublecopy vectors designated DCT5A, DCT5B and DCT5C (see WO 90/13641).

Sense or antisense oligonucleotides also may be introduced into a cellcontaining the target nucleotide sequence by formation of a conjugatewith a ligand binding molecule, as described in WO 91/04753. Suitableligand binding molecules include, but are not limited to, cell surfacereceptors, growth factors, other cytokines, or other ligands that bindto cell surface receptors. Preferably, conjugation of the ligand bindingmolecule does not substantially interfere with the ability of the ligandbinding molecule to bind to its corresponding molecule or receptor, orblock entry of the sense or antisense oligonucleotide or its conjugatedversion into the cell.

Alternatively, a sense or an antisense oligonucleotide may be introducedinto a cell containing the target nucleic acid sequence by formation ofan oligonucleotide-lipid complex, as described in WO 90/10448. The senseor antisense oligonucleotide-lipid complex is preferably dissociatedwithin the cell by an endogenous lipase.

Antisense or sense RNA or DNA molecules are generally at least about 5bases in length, about 10 bases in length, about 15 bases in length,about 20 bases in length, about 25 bases in length, about 30 bases inlength, about 35 bases in length, about 40 bases in length, about 45bases in length, about 50 bases in length, about 55 bases in length,about 60 bases in length, about 65 bases in length, about 70 bases inlength, about 75 bases in length, about 80 bases in length, about 85bases in length, about 90 bases in length, about 95 bases in length,about 100 bases in length, or more.

The probes may also be employed in PCR techniques to generate a pool ofsequences for identification of closely related PRO coding sequences.

Nucleotide sequences encoding a PRO can also be used to constructhybridization probes for mapping the gene which encodes that PRO and forthe genetic analysis of individuals with genetic disorders. Thenucleotide sequences provided herein may be mapped to a chromosome andspecific regions of a chromosome using known techniques, such as in situhybridization, linkage analysis against known chromosomal markers, andhybridization screening with libraries.

When the coding sequences for PRO encode a protein which binds toanother protein (example, where the PRO is a receptor), the PRO can beused in assays to identify the other proteins or molecules involved inthe binding interaction. By such methods, inhibitors of thereceptor/ligand binding interaction can be identified. Proteins involvedin such binding interactions can also be used to screen for peptide orsmall molecule inhibitors or agonists of the binding interaction. Also,the receptor PRO can be used to isolate correlative ligand(s). Screeningassays can be designed to find lead compounds that mimic the biologicalactivity of a native PRO or a receptor for PRO. Such screening assayswill include assays amenable to high-throughput screening of chemicallibraries, making them particularly suitable for identifying smallmolecule drug candidates. Small molecules contemplated include syntheticorganic or inorganic compounds. The assays can be performed in a varietyof formats, including protein-protein binding assays, biochemicalscreening assays, immunoassays and cell based assays, which are wellcharacterized in the art.

Nucleic acids which encode PRO or its modified forms can also be used togenerate either transgenic animals or “knock out” animals which, inturn, are useful in the development and screening of therapeuticallyuseful reagents. A transgenic animal (e.g., a mouse or rat) is an animalhaving cells that contain a transgene, which transgene was introducedinto the animal or an ancestor of the animal at a prenatal, e.g., anembryonic stage. A transgene is a DNA which is integrated into thegenome of a cell from which a transgenic animal develops. In oneembodiment, cDNA encoding PRO can be used to clone genomic DNA encodingPRO in accordance with established techniques and the genomic sequencesused to generate transgenic animals that contain cells which express DNAencoding PRO. Methods for generating transgenic animals, particularlyanimals such as mice or rats, have become conventional in the art andare described, for example, in U.S. Pat. Nos. 4,736,866 and 4,870,009.Typically, particular cells would be targeted for PRO transgeneincorporation with tissue-specific enhancers. Transgenic animals thatinclude a copy of a transgene encoding PRO introduced into the germ lineof the animal at an embryonic stage can be used to examine the effect ofincreased expression of DNA encoding PRO. Such animals can be used astester animals for reagents thought to confer protection from, forexample, pathological conditions associated with its overexpression. Inaccordance with this facet of the invention, an animal is treated withthe reagent and a reduced incidence of the pathological condition,compared to untreated animals bearing the transgene, would indicate apotential therapeutic intervention for the pathological condition.

Alternatively, non-human homologues of PRO can be used to construct aPRO “knock out” animal which has a defective or altered gene encodingPRO as a result of homologous recombination between the endogenous geneencoding PRO and altered genomic DNA encoding PRO introduced into anembryonic stem cell of the animal. For example, cDNA encoding PRO can beused to clone genomic DNA encoding PRO in accordance with establishedtechniques. A portion of the genomic DNA encoding PRO can be deleted orreplaced with another gene, such as a gene encoding a selectable markerwhich can be used to monitor integration. Typically, several kilobasesof unaltered flanking DNA (both at the 5′ and 3′ ends) are included inthe vector [see e.g., Thomas and Capecchi, Cell, 51:503 (1987) for adescription of homologous recombination vectors]. The vector isintroduced into an embryonic stem cell line (e.g., by electroporation)and cells in which the introduced DNA has homologously recombined withthe endogenous DNA are selected [see e.g., Li et al., Cell, 69:915(1992)]. The selected cells are then injected into a blastocyst of ananimal (e.g., a mouse or rat) to form aggregation chimeras [see e.g.,Bradley, in Teratocarcinomas and Embryonic Stem Cells: A PracticalApproach, E. J. Robertson, ed. (IRL, Oxford, 1987), pp. 113–152]. Achimeric embryo can then be implanted into a suitable pseudopregnantfemale foster animal and the embryo brought to term to create a “knockout” animal. Progeny harboring the homologously recombined DNA in theirgerm cells can be identified by standard techniques and used to breedanimals in which all cells of the animal contain the homologouslyrecombined DNA. Knockout animals can be characterized for instance, fortheir ability to defend against certain pathological conditions and fortheir development of pathological conditions due to absence of the PROpolypeptide.

Nucleic acid encoding the PRO polypeptides may also be used in genetherapy. In gene therapy applications, genes are introduced into cellsin order to achieve in vivo synthesis of a therapeutically effectivegenetic product, for example for replacement of a defective gene. “Genetherapy” includes both conventional gene therapy where a lasting effectis achieved by a single treatment, and the administration of genetherapeutic agents, which involves the one time or repeatedadministration of a therapeutically effective DNA or mRNA. AntisenseRNAs and DNAs can be used as therapeutic agents for blocking theexpression of certain genes in vivo. It has already been shown thatshort antisense oligonucleotides can be imported into cells where theyact as inhibitors, despite their low intracellular concentrations causedby their restricted uptake by the cell membrane. (Zamecnik et al., Proc.Natl. Acad. Sci. USA 83:4143–4146 [1986]). The oligonucleotides can bemodified to enhance their uptake, e.g. by substituting their negativelycharged phosphodiester groups by uncharged groups.

There are a variety of techniques available for introducing nucleicacids into viable cells. The techniques vary depending upon whether thenucleic acid is transferred into cultured cells in vitro, or in vivo inthe cells of the intended host. Techniques suitable for the transfer ofnucleic acid into mammalian cells in vitro include the use of liposomes,electroporation, microinjection, cell fusion, DEAE-dextran, the calciumphosphate precipitation method, etc. The currently preferred in vivogene transfer techniques include transfection with viral (typicallyretroviral) vectors and viral coat protein-liposome mediatedtransfection (Dzau et al., Trends in Biotechnology 11, 205–210 [1993]).In some situations it is desirable to provide the nucleic acid sourcewith an agent that targets the target cells, such as an antibodyspecific for a cell surface membrane protein or the target cell, aligand for a receptor on the target cell, etc. Where liposomes areemployed, proteins which bind to a cell surface membrane proteinassociated with endocytosis may be used for targeting and/or tofacilitate uptake, e.g. capsid proteins or fragments thereof tropic fora particular cell type, antibodies for proteins which undergointernalization in cycling, proteins that target intracellularlocalization and enhance intracellular half-life. The technique ofreceptor-mediated endocytosis is described, for example, by Wu et al.,J. Biol. Chem. 262, 4429–4432 (1987); and Wagner et al., Proc. Natl.Acad. Sci. USA 87, 3410–3414 (1990). For review of gene marking and genetherapy protocols see Anderson et al., Science 256, 808–813 (1992).

The PRO polypeptides described herein may also be employed as molecularweight markers for protein electrophoresis purposes and the isolatednucleic acid sequences may be used for recombinantly expressing thosemarkers.

The nucleic acid molecules encoding the PRO polypeptides or fragmentsthereof described herein are useful for chromosome identification. Inthis regard, there exists an ongoing need to identify new chromosomemarkers, since relatively few chromosome marking reagents, based uponactual sequence data are presently available. Each PRO nucleic acidmolecule of the present invention can be used as a chromosome marker.

The PRO polypeptides and nucleic acid molecules of the present inventionmay also be used for tissue typing, wherein the PRO polypeptides of thepresent invention may be differentially expressed in one tissue ascompared to another. PRO nucleic acid molecules will find use forgenerating probes for PCR, Northern analysis, Southern analysis andWestern analysis.

The PRO polypeptides described herein may also be employed astherapeutic agents. The PRO polypeptides of the present invention can beformulated according to known methods to prepare pharmaceutically usefulcompositions, whereby the PRO product hereof is combined in admixturewith a pharmaceutically acceptable carrier vehicle. Therapeuticformulations are prepared for storage by mixing the active ingredienthaving the desired degree of purity with optional physiologicallyacceptable carriers, excipients or stabilizers (Remington'sPharmaceutical Sciences 16th edition, Osol, A. Ed. (1980)), in the formof lyophilized formulations or aqueous solutions. Acceptable carriers,excipients or stabilizers are nontoxic to recipients at the dosages andconcentrations employed, and include buffers such as phosphate, citrateand other organic acids; antioxidants including ascorbic acid; lowmolecular weight (less than about 10 residues) polypeptides; proteins,such as serum albumin, gelatin or immunoglobulins; hydrophilic polymerssuch as polyvinylpyrrolidone, amino acids such as glycine, glutamine,asparagine, arginine or lysine; monosaccharides, disaccharides and othercarbohydrates including glucose, mannose, or dextrins; chelating agentssuch as EDTA; sugar alcohols such as mannitol or sorbitol; salt-formingcounterions such as sodium; and/or nonionic surfactants such as TWEEN™,PLURONICS™ or PEG.

The formulations to be used for in vivo administration must be sterile.This is readily accomplished by filtration through sterile filtrationmembranes, prior to or following lyophilization and reconstitution.

Therapeutic compositions herein generally are placed into a containerhaving a sterile access port, for example, an intravenous solution bagor vial having a stopper pierceable by a hypodermic injection needle.

The route of administration is in accord with known methods, e.g.injection or infusion by intravenous, intraperitoneal, intracerebral,intramuscular, intraocular, intraarterial or intralesional routes,topical administration, or by sustained release systems.

Dosages and desired drug concentrations of pharmaceutical compositionsof the present invention may vary depending on the particular useenvisioned. The determination of the appropriate dosage or route ofadministration is well within the skill of an ordinary physician. Animalexperiments provide reliable guidance for the determination of effectivedoses for human therapy. Interspecies scaling of effective doses can beperformed following the principles laid down by Mordenti, J. andChappell, W. “The use of interspecies scaling intoxicokinetics” InToxicokinetics and New Drug Development, Yacobi et al., Eds., PergamonPress, New York 1989, pp. 42–96.

When in vivo administration of a PRO polypeptide or agonist orantagonist thereof is employed, normal dosage amounts may vary fromabout 10 ng/kg to up to 100 mg/kg of mammal body weight or more per day,preferably about 1 μg/kg/day to 10 mg/kg/day, depending upon the routeof administration. Guidance as to particular dosages and methods ofdelivery is provided in the literature; see, for example, U.S. Pat. Nos.4,657,760; 5,206,344; or U.S. Pat. No. 5,225,212. It is anticipated thatdifferent formulations will be effective for different treatmentcompounds and different disorders, that administration targeting oneorgan or tissue, for example, may necessitate delivery in a mannerdifferent from that to another organ or tissue.

Where sustained-release administration of a PRO polypeptide is desiredin a formulation with release characteristics suitable for the treatmentof any disease or disorder requiring administration of the PROpolypeptide, microencapsulation of the PRO polypeptide is contemplated.Microencapsulation of recombinant proteins for sustained release hasbeen successfully performed with human growth hormone (rhGH),interferon-(rhIFN- ), interleukin-2, and MN rgp120. Johnson et al., Nat.Med., 2:795–799 (1996); Yasuda, Biomed. Ther., 27:1221–1223 (1993); Horaet al., Bio/Technology, 8:755–758(1990); Cleland, “Design and Productionof Single Immunization Vaccines Using Polylactide PolyglycolideMicrosphere Systems,” in Vaccine Design: The Subunit and AdjuvantApproach, Powell and Newman, eds, (Plenum Press: New York, 1995), pp.439–462; WO 97/03692, WO 96/40072, WO 96/07399; and U.S. Pat. No.5,654,010.

The sustained-release formulations of these proteins were developedusing poly-lactic-coglycolic acid (PLGA) polymer due to itsbiocompatibility and wide range of biodegradable properties. Thedegradation products of PLGA, lactic and glycolic acids, can be clearedquickly within the human body. Moreover, the degradability of thispolymer can be adjusted from months to years depending on its molecularweight and composition. Lewis, “Controlled release of bioactive agentsfrom lactide/glycolide polymer,” in: M. Chasin and R. Langer (Eds.),Biodegradable Polymers as Drug Delivery Systems (Marcel Dekker: NewYork, 1990), pp. 1–41.

This invention encompasses methods of screening compounds to identifythose that mimic the PRO polypeptide (agonists) or prevent the effect ofthe PRO polypeptide (antagonists). Screening assays for antagonist drugcandidates are designed to identify compounds that bind or complex withthe PRO polypeptides encoded by the genes identified herein, orotherwise interfere with the interaction of the encoded polypeptideswith other cellular proteins. Such screening assays will include assaysamenable to high-throughput screening of chemical libraries, making themparticularly suitable for identifying small molecule drug candidates.

The assays can be performed in a variety of formats, includingprotein-protein binding assays, biochemical screening assays,immunoassays, and cell-based assays, which are well characterized in theart.

All assays for antagonists are common in that they call for contactingthe drug candidate with a PRO polypeptide encoded by a nucleic acididentified herein under conditions and for a time sufficient to allowthese two components to interact.

In binding assays, the interaction is binding and the complex formed canbe isolated or detected in the reaction mixture. In a particularembodiment, the PRO polypeptide encoded by the gene identified herein orthe drug candidate is immobilized on a solid phase, e.g., on amicrotiter plate, by covalent or non-covalent attachments. Non-covalentattachment generally is accomplished by coating the solid surface with asolution of the PRO polypeptide and drying. Alternatively, animmobilized antibody, e.g., a monoclonal antibody, specific for the PROpolypeptide to be immobilized can be used to anchor it to a solidsurface. The assay is performed by adding the non-immobilized component,which may be labeled by a detectable label, to the immobilizedcomponent, e.g., the coated surface containing the anchored component.When the reaction is complete, the non-reacted components are removed,e.g., by washing, and complexes anchored on the solid surface aredetected. When the originally non-immobilized component carries adetectable label, the detection of label immobilized on the surfaceindicates that complexing occurred. Where the originally non-immobilizedcomponent does not carry a label, complexing can be detected, forexample, by using a labeled antibody specifically binding theimmobilized complex.

If the candidate compound interacts with but does not bind to aparticular PRO polypeptide encoded by a gene identified herein, itsinteraction with that polypeptide can be assayed by methods well knownfor detecting protein-protein interactions. Such assays includetraditional approaches, such as, e.g., cross-linking,co-immunoprecipitation, and co-purification through gradients orchromatographic columns. In addition, protein-protein interactions canbe monitored by using a yeast-based genetic system described by Fieldsand co-workers (Fields and Song, Nature (London), 340:245–246 (1989);Chien et al., Proc. Natl. Acad. Sci. USA, 88:9578–9582 (1991)) asdisclosed by Chevray and Nathans, Proc. Natl. Acad. Sci. USA, 89:5789–5793 (1991). Many transcriptional activators, such as yeast GAL4,consist of two physically discrete modular domains, one acting as theDNA-binding domain, the other one functioning as thetranscription-activation domain. The yeast expression system describedin the foregoing publications (generally referred to as the “two-hybridsystem”) takes advantage of this property, and employs two hybridproteins, one in which the target protein is fused to the DNA-bindingdomain of GAL4, and another, in which candidate activating proteins arefused to the activation domain. The expression of a GAL1-lacZ reportergene under control of a GAL4-activated promoter depends onreconstitution of GAL4 activity via protein-protein interaction.Colonies containing interacting polypeptides are detected with achromogenic substrate for β-galactosidase. A complete kit (MATCHMAKER™)for identifying protein-protein interactions between two specificproteins using the two-hybrid technique is commercially available fromClontech. This system can also be extended to map protein domainsinvolved in specific protein interactions as well as to pinpoint aminoacid residues that are crucial for these interactions.

Compounds that interfere with the interaction of a gene encoding a PROpolypeptide identified herein and other intra- or extracellularcomponents can be tested as follows: usually a reaction mixture isprepared containing the product of the gene and the intra- orextracellular component under conditions and for a time allowing for theinteraction and binding of the two products. To test the ability of acandidate compound to inhibit binding, the reaction is run in theabsence and in the presence of the test compound. In addition, a placebomay be added to a third reaction mixture, to serve as positive control.The binding (complex formation) between the test compound and the intra-or extracellular component present in the mixture is monitored asdescribed hereinabove. The formation of a complex in the controlreaction(s) but not in the reaction mixture containing the test compoundindicates that the test compound interferes with the interaction of thetest compound and its reaction partner.

To assay for antagonists, the PRO polypeptide may be added to a cellalong with the compound to be screened for a particular activity and theability of the compound to inhibit the activity of interest in thepresence of the PRO polypeptide indicates that the compound is anantagonist to the PRO polypeptide. Alternatively, antagonists may bedetected by combining the PRO polypeptide and a potential antagonistwith membrane-bound PRO polypeptide receptors or recombinant receptorsunder appropriate conditions for a competitive inhibition assay. The PROpolypeptide can be labeled, such as by radioactivity, such that thenumber of PRO polypeptide molecules bound to the receptor can be used todetermine the effectiveness of the potential antagonist. The geneencoding the receptor can be identified by numerous methods known tothose of skill in the art, for example, ligand panning and FACS sorting.Coligan et al., Current Protocols in Immun., 1(2): Chapter 5 (1991).Preferably, expression cloning is employed wherein polyadenylated RNA isprepared from a cell responsive to the PRO polypeptide and a cDNAlibrary created from this RNA is divided into pools and used totransfect COS cells or other cells that are not responsive to the PROpolypeptide. Transfected cells that are grown on glass slides areexposed to labeled PRO polypeptide. The PRO polypeptide can be labeledby a variety of means including iodination or inclusion of a recognitionsite for a site-specific protein kinase. Following fixation andincubation, the slides are subjected to autoradiographic analysis.Positive pools are identified and sub-pools are prepared andre-transfected using an interactive sub-pooling and re-screeningprocess, eventually yielding a single clone that encodes the putativereceptor.

As an alternative approach for receptor identification, labeled PROpolypeptide can be photoaffinity-linked with cell membrane or extractpreparations that express the receptor molecule. Cross-linked materialis resolved by PAGE and exposed to X-ray film. The labeled complexcontaining the receptor can be excised, resolved into peptide fragments,and subjected to protein micro-sequencing. The amino acid sequenceobtained from micro-sequencing would be used to design a set ofdegenerate oligonucleotide probes to screen a cDNA library to identifythe gene encoding the putative receptor.

In another assay for antagonists, mammalian cells or a membranepreparation expressing the receptor would be incubated with labeled PROpolypeptide in the presence of the candidate compound. The ability ofthe compound to enhance or block this interaction could then bemeasured.

More specific examples of potential antagonists include anoligonucleotide that binds to the fusions of immunoglobulin with PROpolypeptide, and, in particular, antibodies including, withoutlimitation, poly- and monoclonal antibodies and antibody fragments,single-chain antibodies, anti-idiotypic antibodies, and chimeric orhumanized versions of such antibodies or fragments, as well as humanantibodies and antibody fragments. Alternatively, a potential antagonistmay be a closely related protein, for example, a mutated form of the PROpolypeptide that recognizes the receptor but imparts no effect, therebycompetitively inhibiting the action of the PRO polypeptide.

Another potential PRO polypeptide antagonist is an antisense RNA or DNAconstruct prepared using antisense technology, where, e.g., an antisenseRNA or DNA molecule acts to block directly the translation of mRNA byhybridizing to targeted mRNA and preventing protein translation.Antisense technology can be used to control gene expression throughtriple-helix formation or antisense DNA or RNA, both of which methodsare based on binding of a polynucleotide to DNA or RNA. For example, the5′ coding portion of the polynucleotide sequence, which encodes themature PRO polypeptides herein, is used to design an antisense RNAoligonucleotide of from about 10 to 40 base pairs in length. A DNAoligonucleotide is designed to be complementary to a region of the geneinvolved in transcription (triple helix—see Lee et al., Nucl. AcidsRes., 6:3073 (1979); Cooney et al., Science, 241:456 (1988); Dervan etal., Science, 251:1360 (1991)), thereby preventing transcription and theproduction of the PRO polypeptide. The antisense RNA oligonucleotidehybridizes to the mRNA in vivo and blocks translation of the mRNAmolecule into the PRO polypeptide (antisense—Okano, Neurochem., 56:560(1991); Oligodeoxynucleotides as Antisense Inhibitors of Gene Expression(CRC Press: Boca Raton, Fla., 1988). The oligonucleotides describedabove can also be delivered to cells such that the antisense RNA or DNAmay be expressed in vivo to inhibit production of the PRO polypeptide.When antisense DNA is used, oligodeoxyribonucleotides derived from thetranslation-initiation site, e.g., between about −10 and +10 positionsof the target gene nucleotide sequence, are preferred.

Potential antagonists include small molecules that bind to the activesite, the receptor binding site, or growth factor or other relevantbinding site of the PRO polypeptide, thereby blocking the normalbiological activity of the PRO polypeptide. Examples of small moleculesinclude, but are not limited to, small peptides or peptide-likemolecules, preferably soluble peptides, and synthetic non-peptidylorganic or inorganic compounds.

Ribozymes are enzymatic RNA molecules capable of catalyzing the specificcleavage of RNA. Ribozymes act by sequence-specific hybridization to thecomplementary target RNA, followed by endonucleolytic cleavage. Specificribozyme cleavage sites within a potential RNA target can be identifiedby known techniques. For further details see, e.g., Rossi, CurrentBiology, 4:469–471 (1994), and PCT publication No. WO 97/33551(published Sep. 18, 1997).

Nucleic acid molecules in triple-helix formation used to inhibittranscription should be single-stranded and composed ofdeoxynucleotides. The base composition of these oligonucleotides isdesigned such that it promotes triple-helix formation via Hoogsteenbase-pairing rules, which generally require sizeable stretches ofpurines or pyrimidines on one strand of a duplex. For further detailssee, e.g., PCT publication No. WO 97/33551, supra.

These small molecules can be identified by any one or more of thescreening assays discussed hereinabove and/or by any other screeningtechniques well known for those skilled in the art.

Uses of the herein disclosed molecules may also be based upon thepositive functional assay hits disclosed and described below.

F. Anti-PRO Antibodies

The present invention further provides anti-PRO antibodies. Exemplaryantibodies include polyclonal, monoclonal, humanized, bispecific, andheteroconjugate antibodies.

1. Polyclonal Antibodies

The anti-PRO antibodies may comprise polyclonal antibodies. Methods ofpreparing polyclonal antibodies are known to the skilled artisan.Polyclonal antibodies can be raised in a mammal, for example, by one ormore injections of an immunizing agent and, if desired, an adjuvant.Typically, the immunizing agent and/or adjuvant will be injected in themammal by multiple subcutaneous or intraperitoneal injections. Theimmunizing agent may include the PRO polypeptide or a fusion proteinthereof. It may be useful to conjugate the immunizing agent to a proteinknown to be immunogenic in the mammal being immunized. Examples of suchimmunogenic proteins include but are not limited to keyhole limpethemocyanin, serum albumin, bovine thyroglobulin, and soybean trypsininhibitor. Examples of adjuvants which may be employed include Freund'scomplete adjuvant and MPL-TDM adjuvant (monophosphoryl Lipid A,synthetic trehalose dicorynomycolate). The immunization protocol may beselected by one skilled in the art without undue experimentation.

2. Monoclonal Antibodies

The anti-PRO antibodies may, alternatively, be monoclonal antibodies.Monoclonal antibodies may be prepared using hybridoma methods, such asthose described by Kohler and Milstein, Nature, 256:495 (1975). In ahybridoma method, a mouse, hamster, or other appropriate host animal, istypically immunized with an immunizing agent to elicit lymphocytes thatproduce or are capable of producing antibodies that will specificallybind to the immunizing agent. Alternatively, the lymphocytes may beimmunized in vitro.

The immunizing agent will typically include the PRO polypeptide or afusion protein thereof. Generally, either peripheral blood lymphocytes(“PBLs”) are used if cells of human origin are desired, or spleen cellsor lymph node cells are used if non-human mammalian sources are desired.The lymphocytes are then fused with an immortalized cell line using asuitable fusing agent, such as polyethylene glycol, to form a hybridomacell [Goding, Monoclonal Antibodies: Principles and Practice, AcademicPress, (1986) pp. 59–103]. Immortalized cell lines are usuallytransformed mammalian cells, particularly myeloma cells of rodent,bovine and human origin. Usually, rat or mouse myeloma cell lines areemployed. The hybridoma cells may be cultured in a suitable culturemedium that preferably contains one or more substances that inhibit thegrowth or survival of the unfused, immortalized cells. For example, ifthe parental cells lack the enzyme hypoxanthine guanine phosphoribosyltransferase (HGPRT or HPRT), the culture medium for the hybridomastypically will include hypoxanthine, aminopterin, and thymidine (“HATmedium”), which substances prevent the growth of HGPRT-deficient cells.

Preferred immortalized cell lines are those that fuse efficiently,support stable high level expression of antibody by the selectedantibody-producing cells, and are sensitive to a medium such as HATmedium. More preferred immortalized cell lines are murine myeloma lines,which can be obtained, for instance, from the Salk Institute CellDistribution Center, San Diego, Calif. and the American Type CultureCollection, Manassas, Va. Human myeloma and mouse-human heteromyelomacell lines also have been described for the production of humanmonoclonal antibodies [Kozbor, J. Immunol., 133:3001 (1984); Brodeur etal., Monoclonal Antibody Production Techniques and Applications, MarcelDekker, Inc., New York, (1987) pp. 51–63].

The culture medium in which the hybridoma cells are cultured can then beassayed for the presence of monoclonal antibodies directed against PRO.Preferably, the binding specificity of monoclonal antibodies produced bythe hybridoma cells is determined by immunoprecipitation or by an invitro binding assay, such as radioimmunoassay (RIA) or enzyme-linkedimmunoabsorbent assay (ELISA). Such techniques and assays are known inthe art. The binding affinity of the monoclonal antibody can, forexample, be determined by the Scatchard analysis of Munson and Pollard,Anal. Biochem., 107:220 (1980).

After the desired hybridoma cells are identified, the clones may besubcloned by limiting dilution procedures and grown by standard methods[Goding, supra]. Suitable culture media for this purpose include, forexample, Dulbecco's Modified Eagle's Medium and RPMI-1640 medium.Alternatively, the hybridoma cells may be grown in vivo as ascites in amammal.

The monoclonal antibodies secreted by the subclones may be isolated orpurified from the culture medium or ascites fluid by conventionalimmunoglobulin purification procedures such as, for example, proteinA-Sepharose, hydroxylapatite chromatography, gel electrophoresis,dialysis, or affinity chromatography.

The monoclonal antibodies may also be made by recombinant DNA methods,such as those described in U.S. Pat. No. 4,816,567. DNA encoding themonoclonal antibodies of the invention can be readily isolated andsequenced using conventional procedures (e.g., by using oligonucleotideprobes that are capable of binding specifically to genes encoding theheavy and light chains of murine antibodies). The hybridoma cells of theinvention serve as a preferred source of such DNA. Once isolated, theDNA may be placed into expression vectors, which are then transfectedinto host cells such as simian COS cells, Chinese hamster ovary (CHO)cells, or myeloma cells that do not otherwise produce immunoglobulinprotein, to obtain the synthesis of monoclonal antibodies in therecombinant host cells. The DNA also may be modified, for example, bysubstituting the coding sequence for human heavy and light chainconstant domains in place of the homologous murine sequences [U.S. Pat.No. 4,816,567; Morrison et al., supra] or by covalently joining to theimmunoglobulin coding sequence all or part of the coding sequence for anon-immunoglobulin polypeptide. Such a non-immunoglobulin polypeptidecan be substituted for the constant domains of an antibody of theinvention, or can be substituted for the variable domains of oneantigen-combining site of an antibody of the invention to create achimeric bivalent antibody.

The antibodies may be monovalent antibodies. Methods for preparingmonovalent antibodies are well known in the art. For example, one methodinvolves recombinant expression of immunoglobulin light chain andmodified heavy chain. The heavy chain is truncated generally at anypoint in the Fc region so as to prevent heavy chain crosslinking.Alternatively, the relevant cysteine residues are substituted withanother amino acid residue or are deleted so as to prevent crosslinking.

In vitro methods are also suitable for preparing monovalent antibodies.Digestion of antibodies to produce fragments thereof, particularly, Fabfragments, can be accomplished using routine techniques known in theart.

3. Human and Humanized Antibodies

The anti-PRO antibodies of the invention may further comprise humanizedantibodies or human antibodies. Humanized forms of non-human (e.g.,murine) antibodies are chimeric immunoglobulins, immunoglobulin chainsor fragments thereof (such as Fv, Fab, Fab′, F(ab′)₂ or otherantigen-binding subsequences of antibodies) which contain minimalsequence derived from non-human immunoglobulin. Humanized antibodiesinclude human immunoglobulins (recipient antibody) in which residuesfrom a complementary determining region (CDR) of the recipient arereplaced by residues from a CDR of a non-human species (donor antibody)such as mouse, rat or rabbit having the desired specificity, affinityand capacity. In some instances, Fv framework residues of the humanimmunoglobulin are replaced by corresponding non-human residues.Humanized antibodies may also comprise residues which are found neitherin the recipient antibody nor in the imported CDR or frameworksequences. In general, the humanized antibody will comprisesubstantially all of at least one, and typically two, variable domains,in which all or substantially all of the CDR regions correspond to thoseof a non-human immunoglobulin and all or substantially all of the FRregions are those of a human immunoglobulin consensus sequence. Thehumanized antibody optimally also will comprise at least a portion of animmunoglobulin constant region (Fc), typically that of a humanimmunoglobulin [Jones et al., Nature, 321:522–525 (1986); Riechmann etal., Nature, 332:323–329 (1988); and Presta, Curr. Op. Struct. Biol.,2:593–596 (1992)].

Methods for humanizing non-human antibodies are well known in the art.Generally, a humanized antibody has one or more amino acid residuesintroduced into it from a source which is non-human. These non-humanamino acid residues are often referred to as “import” residues, whichare typically taken from an “import” variable domain. Humanization canbe essentially performed following the method of Winter and co-workers[Jones et al., Nature, 321:522–525 (1986); Riechmann et al., Nature,332:323–327 (1988); Verhoeyen et al., Science, 239:1534–1536 (1988)], bysubstituting rodent CDRs or CDR sequences for the correspondingsequences of a human antibody. Accordingly, such “humanized” antibodiesare chimeric antibodies (U.S. Pat. No. 4,816,567), wherein substantiallyless than an intact human variable domain has been substituted by thecorresponding sequence from a non-human species. In practice, humanizedantibodies are typically human antibodies in which some CDR residues andpossibly some FR residues are substituted by residues from analogoussites in rodent antibodies.

Human antibodies can also be produced using various techniques known inthe art, including phage display libraries [Hoogenboom and Winter, J.Mol. Biol., 227:381 (1991); Marks et al., J. Mol. Biol., 222:581(1991)]. The techniques of Cole et al. and Boerner et al. are alsoavailable for the preparation of human monoclonal antibodies (Cole etal., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, p. 77(1985) and Boerner et al., J. Immunol., 147(1):86–95 (1991)]. Similarly,human antibodies can be made by introducing of human immunoglobulin lociinto transgenic animals, e.g., mice in which the endogenousimmunoglobulin genes have been partially or completely inactivated. Uponchallenge, human antibody production is observed, which closelyresembles that seen in humans in all respects, including generearrangement, assembly, and antibody repertoire. This approach isdescribed, for example, in U.S. Pat. Nos. 5,545,807; 5,545,806;5,569,825; 5,625,126; 5,633,425; 5,661,016, and in the followingscientific publications: Marks et al., Bio/Technology 10, 779–783(1992); Lonberg et al., Nature 368 856–859 (1994); Morrison, Nature 368,812–13 (1994); Fishwild et al., Nature Biotechnology 14, 845–51 (1996);Neuberger, Nature Biotechnology 14, 826 (1996); Lonberg and Huszar,Intern. Rev. Immunol. 13 65–93 (1995).

4. Bisuecific Antibodies

Bispecific antibodies are monoclonal, preferably human or humanized,antibodies that have binding specificities for at least two differentantigens. In the present case, one of the binding specificities is forthe PRO, the other one is for any other antigen, and preferably for acell-surface protein or receptor or receptor subunit.

Methods for making bispecific antibodies are known in the art.Traditionally, the recombinant production of bispecific antibodies isbased on the co-expression of two immunoglobulin heavy-chain/light-chainpairs, where the two heavy chains have different specificities [Milsteinand Cuello, Nature, 305:537–539 (1983)]. Because of the randomassortment of immunoglobulin heavy and light chains, these hybridomas(quadromas) produce a potential mixture of ten different antibodymolecules, of which only one has the correct bispecific structure. Thepurification of the correct molecule is usually accomplished by affinitychromatography steps. Similar procedures are disclosed in WO 93/08829,published 13, May 1993, and in Traunecker et al., EMBO J., 10:3655–3659(1991).

Antibody variable domains with the desired binding specificities(antibody-antigen combining sites) can be fused to immunoglobulinconstant domain sequences. The fusion preferably is with animmunoglobulin heavy-chain constant domain, comprising at least part ofthe hinge, CH2, and CH3 regions. It is preferred to have the firstheavy-chain constant region (CH1) containing the site necessary forlight-chain binding present in at least one of the fusions. DNAsencoding the immunoglobulin heavy-chain fusions and, if desired, theimmunoglobulin light chain, are inserted into separate expressionvectors, and are co-transfected into a suitable host organism. Forfurther details of generating bispecific antibodies see, for example,Suresh et al., Methods in Enzymology, 121:210 (1986).

According to another approach described in WO 96/27011, the interfacebetween a pair of antibody molecules can be engineered to maximize thepercentage of heterodimers which are recovered from recombinant cellculture. The preferred interface comprises at least a part of the CH3region of an antibody constant domain. In this method, one or more smallamino acid side chains from the interface of the first antibody moleculeare replaced with larger side chains (e.g. tyrosine or tryptophan).Compensatory “cavities” of identical or similar size to the large sidechain(s) are created on the interface of the second antibody molecule byreplacing large amino acid side chains with smaller ones (e.g. alanineor threonine). This provides a mechanism for increasing the yield of theheterodimer over other unwanted end-products such as homodimers.

Bispecific antibodies can be prepared as full length antibodies orantibody fragments (e.g. F(ab′)₂ bispecific antibodies). Techniques forgenerating bispecific antibodies from antibody fragments have beendescribed in the literature. For example, bispecific antibodies can beprepared can be prepared using chemical linkage. Brennan et al., Science229:81 (1985) describe a procedure wherein intact antibodies areproteolytically cleaved to generate F(ab′)₂ fragments. These fragmentsare reduced in the presence of the dithiol complexing agent sodiumarsenite to stabilize vicinal dithiols and prevent intermoleculardisulfide formation. The Fab′ fragments generated are then converted tothionitrobenzoate (TNB) derivatives. One of the Fab′-TNB derivatives isthen reconverted to the Fab′-thiol by reduction with mercaptoethylamineand is mixed with an equimolar amount of the other Fab′-TNB derivativeto form the bispecific antibody. The bispecific antibodies produced canbe used as agents for the selective immobilization of enzymes.

Fab′ fragments may be directly recovered from E. coli and chemicallycoupled to form bispecific antibodies. Shalaby et al., J. Exp. Med.175:217–225 (1992) describe the production of a fully humanizedbispecific antibody F(ab′)₂ molecule. Each Fab′ fragment was separatelysecreted from E. coli and subjected to directed chemical coupling invitro to form the bispecific antibody. The bispecific antibody thusformed was able to bind to cells over expressing the ErbB2 receptor andnormal human T cells, as well as trigger the lytic activity of humancytotoxic lymphocytes against human breast tumor targets.

Various technique for making and isolating bispecific antibody fragmentsdirectly from recombinant cell culture have also been described. Forexample, bispecific antibodies have been produced using leucine zippers.Kostelny et al., J. Immunol. 148(5):1547–1553 (1992). The leucine zipperpeptides from the Fos and Jun proteins were linked to the Fab′ portionsof two different antibodies by gene fusion. The antibody homodimers werereduced at the hinge region to form monomers and then reoxidized to formthe antibody heterodimers. This method can also be utilized for theproduction of antibody homodimers. The “diabody” technology described byHollinger et al., Proc. Natl. Acad. Sci. USA 90:6444–6448 (1993) hasprovided an alternative mechanism for making bispecific antibodyfragments. The fragments comprise a heavy-chain variable domain (V_(H))connected to a light-chain variable domain (V_(L)) by a linker which istoo short to allow pairing between the two domains on the same chain.Accordingly, the V_(H) and V_(L) domains of one fragment are forced topair with the complementary V_(L) and V_(H) domains of another fragment,thereby forming two antigen-binding sites. Another strategy for makingbispecific antibody fragments by the use of single-chain Fv (sFv) dimershas also been reported. See, Gruber et al., J. Immunol. 152:5368 (1994).Antibodies with more than two valencies are contemplated. For example,trispecific antibodies can be prepared. Tutt et al., J. Immunol. 147:60(1991).

Exemplary bispecific antibodies may bind to two different epitopes on agiven PRO polypeptide herein. Alternatively, an anti-PRO polypeptide armmay be combined with an arm which binds to a triggering molecule on aleukocyte such as a T-cell receptor molecule (e.g. CD2, CD3, CD28, orB7), or Fc receptors for IgG (FcγR), such as FcγRI (CD64), FcγRII (CD32)and FcγRIII (CD16) so as to focus cellular defense mechanisms to thecell expressing the particular PRO polypeptide. Bispecific antibodiesmay also be used to localize cytotoxic agents to cells which express aparticular PRO polypeptide. These antibodies possess a PRO-binding armand an arm which binds a cytotoxic agent or a radionuclide chelator,such as EOTUBE, DPTA, DOTA, or TETA. Another bispecific antibody ofinterest binds the PRO polypeptide and further binds tissue factor (TF).

5. Heteroconjugate Antibodies

Heteroconjugate antibodies are also within the scope of the presentinvention. Heteroconjugate antibodies are composed of two covalentlyjoined antibodies. Such antibodies have, for example, been proposed totarget immune system cells to unwanted cells [U.S. Pat. No. 4,676,980],and for treatment of HIV infection [WO 91/00360; WO 92/200373; EP03089]. It is contemplated that the antibodies may be prepared in vitrousing known methods in synthetic protein chemistry, including thoseinvolving crosslinking agents. For example, immunotoxins may beconstructed using a disulfide exchange reaction or by forming athioether bond. Examples of suitable reagents for this purpose includeiminothiolate and methyl-4-mercaptobutyrimidate and those disclosed, forexample, in U.S. Pat. No. 4,676,980.

6. Effector Function Engineering

It may be desirable to modify the antibody of the invention with respectto effector function, so as to enhance, e.g., the effectiveness of theantibody in treating cancer. For example, cysteine residue(s) may beintroduced into the Fc region, thereby allowing interchain disulfidebond formation in this region. The homodimeric antibody thus generatedmay have improved internalization capability and/or increasedcomplement-mediated cell killing and antibody-dependent cellularcytotoxicity (ADCC). See Caron et al., J. Exp. Med., 176:1191–1195(1992) and Shopes, J. Immunol., 148:2918–2922(1992).Homodimeric antibodies with enhanced anti-tumor activity may also beprepared using heterobifunctional cross-linkers as described in Wolff etal. Cancer Research, 53: 2560–2565 (1993). Alternatively, an antibodycan be engineered that has dual Fc regions and may thereby have enhancedcomplement lysis and ADCC capabilities. See Stevenson et al.,Anti-Cancer Drug Design. 3: 219–230 (1989).

7. Immnunoconjugates

The invention also pertains to immunoconjugates comprising an antibodyconjugated to a cytotoxic agent such as a chemotherapeutic agent, toxin(e.g., an enzymatically active toxin of bacterial, fungal, plant, oranimal origin, or fragments thereof), or a radioactive isotope (i.e., aradioconjugate).

Chemotherapeutic agents useful in the generation of suchimmunoconjugates have been described above. Enzymatically active toxinsand fragments thereof that can be used include diphtheria A chain,nonbinding active fragments of diphtheria toxin, exotoxin A chain (fromPseudomonas aeruginosa), ricin A chain, abrin A chain, modeccin A chain,alpha-sarcin, Aleurites fordii proteins, dianthin proteins, Phytolacaamericana proteins (PAPI, PAPII, and PAP-S), momordica charantiainhibitor, curcin, crotin, sapaonaria officinalis inhibitor, gelonin,mitogellin, restrictocin, phenomycin, enomycin, and the tricothecenes. Avariety of radionuclides are available for the production ofradioconjugated antibodies. Examples include ²¹²Bi, ¹³¹I, ¹³¹In, ⁹⁰Y,and ₁₈₆Re. Conjugates of the antibody and cytotoxic agent are made usinga variety of bifunctional protein-coupling agents such asN-succinimidyl-3-(2-pyridyldithiol) propionate (SPDP), iminothiolane(IT), bifunctional derivatives of imidoesters (such as dimethyladipimidate HCL), active esters (such as disuccininidyl suberate),aldehydes (such as glutareldehyde), bis-azido compounds (such as bis(p-azidobenzoyl) hexanediamine), bis-diazonium derivatives (such asbis-(p-diazoniumbenzoyl)-ethylenediamine), diisocyanates (such astolyene 2,6-diisocyanate), and bis-active fluorine compounds (such as1,5-difluoro-2,4-dinitrobenzene). For example, a ricin immunotoxin canbe prepared as described in Vitetta et al., Science, 238: 1098 (1987).Carbon-14-labeled 1-isothiocyanatobenzyl-3-methyldiethylenetriaminepentaacetic acid (MX-DTPA) is an exemplary chelating agent forconjugation of radionucleotide to the antibody. See WO94/11026.

In another embodiment, the antibody may be conjugated to a “receptor”(such streptavidin) for utilization in tumor pretargeting wherein theantibody-receptor conjugate is administered to the patient, followed byremoval of unbound conjugate from the circulation using a clearing agentand then administration of a “ligand” (e.g., avidin) that is conjugatedto a cytotoxic agent (e.g., a radionucleotide).

8. Immunoliposomes

The antibodies disclosed herein may also be formulated asimmunoliposomes. Liposomes containing the antibody are prepared bymethods known in the art, such as described in Epstein et al., Proc.Natl. Acad. Sci. USA, 82: 3688 (1985); Hwang et al., Proc. Natl Acad.Sci. USA, 77: 4030 (1980); and U.S. Pat. Nos. 4,485,045 and 4,544,545.Liposomes with enhanced circulation time are disclosed in U.S. Pat. No.5,013,556.

Particularly useful liposomes can be generated by the reverse-phaseevaporation method with a lipid composition comprisingphosphatidylcholine, cholesterol, and PEG-derivatizedphosphatidylethanolamine (PEG-PE). Liposomes are extruded throughfilters of defined pore size to yield liposomes with the desireddiameter. Fab′ fragments of the antibody of the present invention can beconjugated to the liposomes as described in Martin et al ., J. Biol.Chem., 257: 286–288 (1982) via a disulfide-interchange reaction. Achemotherapeutic agent (such as Doxorubicin) is optionally containedwithin the liposome. See Gabizon et al., J. National Cancer Inst.,81(19): 1484 (1989).

9. Pharmaceutical Compositions of Antibodies

Antibodies specifically binding a PRO polypeptide identified herein, aswell as other molecules identified by the screening assays disclosedhereinbefore, can be administered for the treatment of various disordersin the form of pharmaceutical compositions.

If the PRO polypeptide is intracellular and whole antibodies are used asinhibitors, internalizing antibodies are preferred. However,lipofections or liposomes can also be used to deliver the antibody, oran antibody fragment, into cells. Where antibody fragments are used, thesmallest inhibitory fragment that specifically binds to the bindingdomain of the target protein is preferred. For example, based upon thevariable-region sequences of an antibody, peptide molecules can bedesigned that retain the ability to bind the target protein sequence.Such peptides can be synthesized chemically and/or produced byrecombinant DNA technology. See, e.g., Marasco et al., Proc. Natl. Acad.Sci. USA, 90: 7889–7893 (1993). The formulation herein may also containmore than one active compound as necessary for the particular indicationbeing treated, preferably those with complementary activities that donot adversely affect each other. Alternatively, or in addition, thecomposition may comprise an agent that enhances its function, such as,for example, a cytotoxic agent, cytokine, chemotherapeutic agent, orgrowth-inhibitory agent. Such molecules are suitably present incombination in amounts that are effective for the purpose intended.

The active ingredients may also be entrapped in microcapsules prepared,for example, by coacervation techniques or by interfacialpolymerization, for example, hydroxymethylcellulose orgelatin-microcapsules and poly-(methylmethacylate) microcapsules,respectively, in colloidal drug delivery systems (for example,liposomes, albumin microspheres, microemulsions, nano-particles, andnanocapsules) or in macroemulsions. Such techniques are disclosed inRemington's Pharmaceutical Sciences, supra.

The formulations to be used for in vivo administration must be sterile.This is readily accomplished by filtration through sterile filtrationmembranes.

Sustained-release preparations may be prepared. Suitable examples ofsustained-release preparations include semipermeable matrices of solidhydrophobic polymers containing the antibody, which matrices are in theform of shaped articles, e.g., films, or microcapsules. Examples ofsustained-release matrices include polyesters, hydrogels (for example,poly(2-hydroxyethyl-methacrylate), or poly(vinylalcohol)), polylactides(U.S. Pat. No. 3,773,919), copolymers of L-glutamic acid andγethyl-L-glutamate, non-degradable ethylene-vinyl acetate, degradablelactic acid-glycolic acid copolymers such as the LUPRON DEPOT™(injectable microspheres composed of lactic acid-glycolic acid copolymerand leuprolide acetate), and poly-D-(−)-3-hydroxybutyric acid. Whilepolymers such as ethylene-vinyl acetate and lactic acid-glycolic acidenable release of molecules for over 100 days, certainhydrogels releaseproteins for shorter time periods. When encapsulated antibodies remainin the body for a long time, they may denature or aggregate as a resultof exposure to moisture at 37° C., resulting in a loss of biologicalactivity and possible changes in immunogenicity. Rational strategies canbe devised for stabilization depending on the mechanism involved. Forexample, if the aggregation mechanism is discovered to be intermolecularS—S bond formation through thio-disulfide interchange, stabilization maybe achieved by modifying sulfhydryl residues, lyophilizing from acidicsolutions, controlling moisture content, using appropriate additives,and developing specific polymer matrix compositions.

G. Uses for Anti-PRO Antibodies

The anti-PRO antibodies of the invention have various utilities. Forexample, anti-PRO antibodies may be used in diagnostic assays for PRO,e.g., detecting its expression in specific cells, tissues, or serum.Various diagnostic assay techniques known in the art may be used, suchas competitive binding assays, direct or indirect sandwich assays andimmunoprecipitation assays conducted in either heterogeneous orhomogeneous phases [Zola, Monoclonal Antibodies: A Manual of Techniques,CRC Press, Inc. (1987) pp. 147–158]. The antibodies used in thediagnostic assays can be labeled with a detectable moiety. Thedetectable moiety should be capable of producing, either directly orindirectly, a detectable signal. For example, the detectable moiety maybe a radioisotope, such as ³H, ¹⁴C, ³²P, ³⁵S, or ¹²⁵I, a fluorescent orchemiluminescent compound, such as fluorescein isothiocyanate,rhodamine, or luciferin, or an enzyme, such as alkaline phosphatase,beta-galactosidase or horseradish peroxidase. Any method known in theart for conjugating the antibody to the detectable moiety may beemployed, including those methods described by Hunter et al., Nature,144:945 (1962); David et al., Biochemistry, 13:1014 (1974); Pain et al.,J. Immunol. Meth., 40:219 (1981); and Nygren, J. Histochem. andCytochem., 30:407 (1982).

Anti-PRO antibodies also are useful for the affinity purification of PROfrom recombinant cell culture or natural sources. In this process, theantibodies against PRO are immobilized on a suitable support, such aSephadex resin or filter paper, using methods well known in the art. Theimmobilized antibody then is contacted with a sample containing the PROto be purified, and thereafter the support is washed with a suitablesolvent that will remove substantially all the material in the sampleexcept the PRO, which is bound to the immobilized antibody. Finally, thesupport is washed with another suitable solvent that will release thePRO from the antibody.

The following examples are offered for illustrative purposes only, andare not intended to limit the scope of the present invention in any way.

All patent and literature references cited in the present specificationare hereby incorporated by reference in their entirety.

EXAMPLES

Commercially available reagents referred to in the examples were usedaccording to manufacturer's instructions unless otherwise indicated. Thesource of those cells identified in the following examples, andthroughout the specification, by ATCC accession numbers is the AmericanType Culture Collection, Manassas, Va.

Example 1 Extracellular Domain Homology Screening to Identify NovelPolypeptides and cDNA Encoding Therefor

The extracellular domain (ECD) sequences (including the secretion signalsequence, if any) from about 950 known secreted proteins from theSwiss-Prot public database were used to search EST databases. The ESTdatabases included public databases (e.g., Dayhoff, GenBank), andproprietary databases (e.g. LIFESEQ™, Incyte Pharmaceuticals, Palo Alto,Calif.). The search was performed using the computer program BLAST orBLAST-2 (Altschul et al., Methods in Enzymology 266:460–480 (1996)) as acomparison of the ECD protein sequences to a 6 frame translation of theEST sequences. Those comparisons with a BLAST score of 70 (or in somecases 90) or greater that did not encode known proteins were clusteredand assembled into consensus DNA sequences with the program “phrap”(Phil Green, University of Washington, Seattle, Wash.).

Using this extracellular domain homology screen, consensus DNA sequenceswere assembled relative to the other identified EST sequences usingphrap. In addition, the consensus DNA sequences obtained were often (butnot always) extended using repeated cycles of BLAST or BLAST-2 and phrapto extend the consensus sequence as far as possible using the sources ofEST sequences discussed above.

Based upon the consensus sequences obtained as described above,oligonucleotides were then synthesized and used to identify by PCR acDNA library that contained the sequence of interest and for use asprobes to isolate a clone of the full-length coding sequence for a PROpolypeptide. Forward and reverse PCR primers generally range from 20 to30 nucleotides and are often designed to give a PCR product of about100–1000 bp in length. The probe sequences are typically 40–55 bp inlength. In some cases, additional oligonucleotides are synthesized whenthe consensus sequence is greater than about 1–1.5 kbp. In order toscreen several libraries for a full-length clone, DNA from the librarieswas screened by PCR amplification, as per Ausubel et al., CurrentProtocols in Molecular Biology, with the PCR primer pair. A positivelibrary was then used to isolate clones encoding the gene of interestusing the probe oligonucleotide and one of the primer pairs.

The cDNA libraries used to isolate the cDNA clones were constructed bystandard methods using commercially available reagents such as thosefrom Invitrogen, San Diego, Calif. The cDNA was primed with oligo dTcontaining a NotI site, linked with blunt to SalI hemikinased adaptors,cleaved with NotI, sized appropriately by gel electrophoresis, andcloned in a defined orientation into a suitable cloning vector (such aspRKB or pRKD; pRK5B is a precursor of pRK5D that does not contain theSfiI site; see, Holmes et al., Science, 253:1278–1280 (1991)) in theunique XhoI and NotI sites.

Example 2 Isolation of cDNA Clones by Amylase Screening

1. Preparation of oligo dT primed cDNA library

mRNA was isolated from a human tissue of interest using reagents andprotocols from Invitrogen, San Diego, Calif. (Fast Track 2). This RNAwas used to generate an oligo dT primed cDNA library in the vector pRK5Dusing reagents and protocols from Life Technologies, Gaithersburg, Md.(Super Script Plasmid System). In this procedure, the double strandedcDNA was sized to greater than 1000 bp and the SalI/NotI linkered cDNAwas cloned into XhoI/NotI cleaved vector. pRK5D is a cloning vector thathas an sp6 transcription initiation site followed by an SfiI restrictionenzyme site preceding the XhoI/NotI cDNA cloning sites.

2. Preparation of Random Primed cDNA Library

A secondary cDNA library was generated in order to preferentiallyrepresent the 5′ ends of the primary cDNA clones. Sp6 RNA was generatedfrom the primary library (described above), and this RNA was used togenerate a random primed cDNA library in the vector pSST-AMY.0 usingreagents and protocols from Life Technologies (Super Script PlasmidSystem, referenced above). In this procedure the double stranded cDNAwas sized to 500–1000 bp, Tinkered with blunt to NotI adaptors, cleavedwith SfiI, and cloned into SfiI/NotI cleaved vector. pSST-AMY.0 is acloning vector that has a yeast alcohol dehydrogenase promoter precedingthe cDNA cloning sites and the mouse amylase sequence (the maturesequence without the secretion signal) followed by the yeast alcoholdehydrogenase terminator, after the cloning sites. Thus, cDNAs clonedinto this vector that are fused in frame with amylase sequence will leadto the secretion of amylase from appropriately transfected yeastcolonies.

3. Transformation and Detection

DNA from the library described in paragraph 2 above was chilled on iceto which was added electrocompetent DH10B bacteria (Life Technologies,20 ml). The bacteria and vector mixture was then electroporated asrecommended by the manufacturer. Subsequently, SOC media (LifeTechnologies, 1 ml) was added and the mixture was incubated at 37° C.for 30 minutes. The transformants were then plated onto 20 standard 150mm LB plates containing ampicillin and incubated for 16 hours (37° C.).Positive colonies were scraped off the plates and the DNA was isolatedfrom the bacterial pellet using standard protocols, e.g. CsCl-gradient.The purified DNA was then carried on to the yeast protocols below.

The yeast methods were divided into three categories: (1) Transformationof yeast with the plasmid/cDNA combined vector; (2) Detection andisolation of yeast clones secreting amylase; and (3) PCR amplificationof the insert directly from the yeast colony and purification of the DNAfor sequencing and further analysis.

The yeast strain used was HD56-5A (ATCC-90785). This strain has thefollowing genotype: MAT alpha, ura3-52, leu2-3, leu2-112, his3-11,his3-15, MAL⁺, SUC⁺, GAL⁺. Preferably, yeast mutants can be employedthat have deficient post-translational pathways. Such mutants may havetranslocation deficient alleles in sec71, sec72, sec62, with truncatedsec71 being most preferred. Alternatively, antagonists (includingantisense nucleotides and/or ligands) which interfere with the normaloperation of these genes, other proteins implicated in this posttranslation pathway (e.g., SEC61p, SEC72p, SEC62p, SEC63p, TDJ1p orSSA1p-4p) or the complex formation of these proteins may also bepreferably employed in combination with the amylase-expressing yeast.

Transformation was performed based on the protocol outlined by Gietz etal., Nucl. Acid. Res., 20:1425 (1992). Transformed cells were theninoculated from agar into YEPD complex media broth (100 ml) and grownovernight at 30° C. The YEPD broth was prepared as described in Kaiseret al., Methods in Yeast Genetics, Cold Spring Harbor Press, Cold SpringHarbor, N.Y., p. 207 (1994). The overnight culture was then diluted toabout 2×10⁶ cells/ml (approx. OD₆₀₀32 0.1) into fresh YEPD broth (500ml) and regrown to 1×10⁷ cells/ml (approx. OD₆₀₀=0.4–0.5).

The cells were then harvested and prepared for transformation bytransfer into GS3 rotor bottles in a Sorval GS3 rotor at 5,000 rpm for 5minutes, the supernatant discarded, and then resuspended into sterilewater, and centrifuged again in 50 ml falcon tubes at 3,500 rpm in aBeckman GS-6KR centrifuge. The supernatant was discarded and the cellswere subsequently washed with LiAc/TE (10 ml, 10 mM Tris-HCl, 1 mM EDTApH 7.5, 100 mM Ii₂OOCCH₃), and resuspended into LiAc/TE (2.5 ml).

Transformation took place by mixing the prepared cells (100 μl) withfreshly denatured single stranded salmon testes DNA (Lofstrand Labs,Gaithersburg, Md.) and transforming DNA (1 μg, vol.<10 μl) in microfugetubes. The mixture was mixed briefly by vortexing, then 40% PEG/TE (600μl, 40% polyethylene glycol-4000, 10 mM Tris-HCl, 1 mM EDTA, 100 mMIi₂OOCCH₃, pH 7.5) was added. This mixture was gently mixed andincubated at 30° C. while agitating for 30 minutes. The cells were thenheat shocked at 42° C. for 15 minutes, and the reaction vesselcentrifuged in a microfuge at 12,000 rpm for 5–10 seconds, decanted andresuspended into TE (500 μl, 10 mM Tris-HCl, 1 mM EDTA pH 7.5) followedby recentrifugation. The cells were then diluted into TE (1 ml) andaliquots (200 μl) were spread onto the selective media previouslyprepared in 150 mm growth plates (VWR).

Alternatively, instead of multiple small reactions, the transformationwas performed using a single, large scale reaction, wherein reagentamounts were scaled up accordingly.

The selective media used was a synthetic complete dextrose agar lackinguracil (SCD-Ura) prepared as described in Kaiser et al., Methods inYeast Genetics, Cold Spring Harbor Press, Cold Spring Harbor, N.Y., p.208–210 (1994). Transformants were grown at 30° C. for 2–3 days.

The detection of colonies secreting amylase was performed by includingred starch in the selective growth media. Starch was coupled to the reddye (Reactive Red-120, Sigma) as per the procedure described by Biely etal., Anal. Biochem., 172:176–179 (1988). The coupled starch wasincorporated into the SCD-Ura agar plates at a final concentration of0.15% (w/v), and was buffered with potassium phosphate to a pH of 7.0(50–100 mM final concentration).

The positive colonies were picked and streaked across fresh selectivemedia (onto 150 mm plates) in order to obtain well isolated andidentifiable single colonies. Well isolated single colonies positive foramylase secretion were detected by direct incorporation of red starchinto buffered SCD-Ura agar. Positive colonies were determined by theirability to break down starch resulting in a clear halo around thepositive colony visualized directly.

4. Isolation of DNA by PCR Amplification

When a positive colony was isolated, a portion of it was picked by atoothpick and diluted into sterile water (30 μl) in a 96 well plate. Atthis time, the positive colonies were either frozen and stored forsubsequent analysis or immediately amplified. An aliquot of cells (5 μl)was used as a template for the PCR reaction in a 25 μl volumecontaining: 0.5 μl Klentaq (Clontech, Palo Alto, Calif.); 4.0 μl 10 mMdNTP's (Perkin Elmer-Cetus); 2.5 μl Kentaq buffer (Clontech); 0.25 μlforward oligo 1; 0.25 μl reverse oligo 2; 12.5 μl distilled water. Thesequence of the forward oligonucleotide 1 was:

5′-TGTAAAACGACGGCCAGTTAAATAGACCTGCAATTATTAATCT-3′ (SEQ ID NO:3)The sequence of reverse oligonucleotide 2 was:

5′-CAGGAAACAGCTATGACCACCTGCACACCTGCAAATCCATT-3′ (SEQ ID NO:4)

PCR was then performed as follows:

a. Denature 92° C., 5 minutes b.  3 cycles of: Denature 92° C., 30seconds Anneal 59° C., 30 seconds Extend 72° C., 60 seconds c.  3 cyclesof: Denature 92° C., 30 seconds Anneal 57° C., 30 seconds Extend 72° C.,60 seconds d. 25 cycles of: Denature 92° C., 30 seconds Anneal 55° C.,30 seconds Extend 72° C., 60 seconds e. Hold  4° C.

The underlined regions of the oligonucleotides annealed to the ADHpromoter region and the amylase region, respectively, and amplified a307 bp region from vector pSST-AMY.0 when no insert was present.Typically, the first 18 nucleotides of the 5′ end of theseoligonucleotides contained annealing sites for the sequencing primers.Thus, the total product of the PCR reaction from an empty vector was 343bp. However, signal sequence-fused cDNA resulted in considerably longernucleotide sequences.

Following the PCR, an aliquot of the reaction (5 μl) was examined byagarose gel electrophoresis in a 1% agarose gel using a Tris-Borate-EDTA(TBE) buffering system as described by Sambrook et al., supra. Clonesresulting in a single strong PCR product larger than 400 bp were furtheranalyzed by DNA sequencing after purification with a 96 Qiaquick PCRclean-up column (Qiagen Inc., Chatsworth, Calif.).

Example 3 Isolation of cDNA Clones Using Signal Algorithm Analysis

Various polypeptide-encoding nucleic acid sequences were identified byapplying a proprietary signal sequence finding algorithm developed byGenentech, Inc. (South San Francisco, Calif.) upon ESTs as well asclustered and assembled EST fragments from public (e.g., GenBank) and/orprivate (LIFESEQ®, Incyte Pharmaceuticals, Inc., Palo Alto, Calif.)databases. The signal sequence algorithm computes a secretion signalscore based on the character of the DNA nucleotides surrounding thefirst and optionally the second methionine codon(s) (ATG) at the 5′-endof the sequence or sequence fragment under consideration. Thenucleotides following the first ATG must code for at least 35unambiguous amino acids without any stop codons. If the first ATG hasthe required amino acids, the second is not examined. If neither meetsthe requirement, the candidate sequence is not scored. In order todetermine whether the EST sequence contains an authentic signalsequence, the DNA and corresponding amino acid sequences surrounding theATG codon are scored using a set of seven sensors (evaluationparameters) known to be associated with secretion signals. Use of thisalgorithm resulted in the identification of numerouspolypeptide-encoding nucleic acid sequences.

Example 4 Isolation of cDNA Clones Encoding Human PRO281

In order to obtain a cDNA clone encoding PRO281, methods described inKlein et al., Proc. Natl. Acad. Sci. USA 93:7108–7113 (1996) wereemployed with the following modifications. Yeast transformation wasperformed with limiting amounts of transforming DNA in order to reducethe number of multiple transformed yeast cells. Instead of plasmidisolation from the yeast followed by transformation of E. coli asdescribed in Klein et al., supra, PCR analysis was performed on singleyeast colonies. PCR primers employed were bipartite in order to amplifythe insert and a small portion of the invertase gene (allowing todetermine that the insert was in frame with invertase) and to add onuniversal sequencing primer sites.

An invertase library was transformed into yeast and positives wereselected on sucrose plates. Positive clones were re-tested and PCRproducts were sequenced. The sequence of one clone, PRO281, wasdetermined to contain a signal peptide coding sequence. Oligonucleotideprimers and probes were designed using the nucleotide sequence ofPRO281. A full length plasmid library of cDNAs from human umbilical veinendothelium tissue was titered and approximately 100,000 cfu were platedin 192 pools of 500 cfu/pool into 96-well round bottom plates. Theplates were sealed and pools were grown overnight at 37° C. with shaking(200 rpm). PCR was performed on the individual cultures using primers.Agarose gel electrophoresis was performed and positive wells wereidentified by visualization of a band of the expected size. Individualpositive clones were obtained by colony lift followed by hybridizationwith ³²P-labeled oligonucleotide. These clones were characterized byPCR, restriction digest, and southern blot analyses.

A full length clone was identified that contained a single open readingframe with an apparent translational initiation site at nucleotidepositions 80–82, and a stop signal at nucleotide positions 1115–1117(FIG. 1, SEQ ID NO:1). The predicted polypeptide precursor is 345 aminoacids long, has a calculated molecular weight of approximately 37,205daltons and an estimated pI of approximately 10.15. Analysis of thefull-length PRO281 sequence shown in FIG. 2 (SEQ ID NO:2) evidences thepresence of the following: a signal peptide from about amino acid 1 toabout amino acid 14, multiple transmembrane domains from about aminoacid position 83 to about amino acid position 105, from about amino acidposition 126 to about amino acid position 146, from about amino acidposition 158 to about amino acid position 177, from about amino acidposition 197 to about amino acid position 216, from about amino acidposition 218 to about amino acid position 238, from about amino acidposition 245 to about amino acid position 265, and from about amino acidposition 271 to about amino acid position 290 and an amino acid sequenceblock having homology to G-protein coupled receptor proteins from aboutamino acid 115 to about amino acid 155. Clone UNQ244 (DNA16422-1209) hasbeen deposited with ATCC on Jun. 2, 1998 and is assigned ATCC depositno. 209929.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST-2 sequence alignment analysis of the full-length sequenceshown in FIG. 2 (SEQ ID NO:2), evidenced significant homology betweenthe PRO281 amino acid sequence and the following Dayhoff sequences:H64634, AF033095_(—)1, B64815, YBHL_(—) ECOLI, EMEQUTR_(—)1,AF064763_(—)3, S53708, A69253, AF035413_(—)12 and S63281.

Example 5 Isolation of cDNA Clones Encoding Human PRO276

In order to obtain a cDNA clone encoding PRO276, methods described inKlein et al., PNAS, 93:7108–7113 (1996) were employed with the followingmodifications. Yeast transformation was performed with limiting amountsof transforming DNA in order to reduce the number of multipletransformed yeast cells. Instead of plasmid isolation from the yeastfollowed by transformation of E. coli as described in Klein et al.,supra, PCR analysis was performed on single yeast colonies. PCR primersemployed were bipartite in order to amplify the insert and a smallportion of the invertase gene (allowing to determine that the insert wasin frame with invertase) and to add on universal sequencing primersites.

An invertase library was transformed into yeast and positives wereselected on sucrose plates. Positive clones were re-tested and PCRproducts were sequenced. The sequence of one clone, PRO276, wasdetermined to contain a signal peptide coding sequence. Oligonucleotideprimers and probes were designed using the nucleotide sequence ofPRO276. A full length plasmid library of cDNAs from human fetal livercells was titered and approximately 100,000 cfu were plated in 192 poolsof 500 cfu/pool into 96-well round bottom plates. The plates were sealedand pools were grown overnight at 37 C. with shaking (200 rpm). PCR wasperformed on the individual cultures using primers. Agarose gelelectrophoresis was performed and positive wells were identified byvisualization of a band of the expected size. Individual positive cloneswere obtained by colony lift followed by hybridization with ³²P-labeledoligonucleotide. These clones were characterized by PCR, restrictiondigest, and southern blot analyses.

A full length clone was identified that contained a single open readingframe with an apparent translational initiation site at nucleotidepositions 180–182 and a stop signal at nucleotide positions 933–935(FIG. 3; SEQ ID NO:5). The predicted polypeptide precursor is 251 aminoacids long has a calculated molecular weight of approximately 28,801daltons and an estimated pI of approximately 9.58. The transmembranedomains are approximately at amino acids 98–116 and 152–172 of thesequence shown in FIG. 4 (SEQ ID NO:6). Clone DNA16435-1208 (UNQ243) hasbeen deposited with the ATCC and is assigned ATCC deposit no. 209930.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST-2 sequence alignment analysis of the full-length sequenceshown in FIG. 4 (SEQ ID NO:6), revealed some sequence identity betweenthe PRO276 amino acid sequence and the following Dayhoff sequences:CEG25D7_(—)2, ATT805_(—)2, S69696, GRHR_RAT, NPCBAABCD_(—)3,AB013149_(—)1, P_R85942 and AP000006_(—)5.

Example 6 Isolation of cDNA Clones Encoding Human PRO189

A clone designated herein as DNA14187 was isolated as described inExample 2 above from a human retina tissue library. The DNA14187sequence is shown in FIG. 7 (SEQ ID NO:9). Based on the DNA14187sequence shown in FIG. 7 (SEQ ID NO:9), oligonucleotides weresynthesized: 1) to identify by PCR a cDNA library that contained thesequence of interest, and 2) for use as probes to isolate a clone of thefull-length coding sequence for PRO189. Forward and reverse PCR primersgenerally range from 20 to 30 nucleotides and are often designed to givea PCR product of about 100–1000 bp in length. The probe sequences aretypically 40–55 bp in length. In order to screen several libraries for afull-length clone, DNA from the libraries was screened by PCRamplification, as per Ausubel et al., Current Protocols in MolecularBiology, with the PCR primer pair. A positive library was then used toisolate clones encoding the gene of interest using the probeoligonucleotide and one of the primer pairs.

A pair of PCR primers (forward and reverse) were synthesized:

forward PCR primer 5′-TTGACCTATACAGAGATTCATC-3′ (SEQ ID NO:1O); andreverse PCR primer 5′-CTAAGAACTTCCCTCAGGATTTT-3′ (SEQ ID NO:11).Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the DNA14187 sequence which had the followingnucleotide sequence:Hybridization Probe

-   5′-ATGAAGATCAATTTCAAGAAGCATGCACTTCTCCTCTTGC-3′ (SEQ ID NO:12).

In order to screen several libraries for a source of a full-lengthclone, DNA from the libraries was screened by PCR amplification with thePCR primer pair identified above. A positive library was then used toisolate clones encoding the PRO189 gene using the probe oligonucleotideand one of the PCR primers.

RNA for construction of the cDNA libraries was isolated from humanretina tissue (LIB94). The cDNA libraries used to isolate the cDNAclones were constructed by standard methods using commercially availablereagents such as those from Invitrogen, San Diego, Calif. The cDNA wasprimed with oligo dT containing a NotI site, linked with blunt to SalIhemikinased adaptors, cleaved with NotI, sized appropriately by gelelectrophoresis, and cloned in a defined orientation into a suitablecloning vector (such as pRKB or pRKD; pRK5B is a precursor of pRK5D thatdoes not contain the SfiI site; see, Holmes et al., Science,253:1278–1280 (1991)) in the unique XhoI and NotI sites.

DNA sequencing of the clones isolated as described above gave thefull-length DNA sequence for PRO189 and the derived protein sequence forPRO189.

The entire nucleotide sequence of DNA21624-1391 is shown in FIG. 5 (SEQID NO:7). Clone DNA21624-1391 contains a single open reading frame withan apparent translational initiation site at nucleotide positions200–202 and ending at the stop codon at nucleotide positions 1301–1303(FIG. 5). The predicted polypeptide precursor is 367 amino acids long(FIG. 6). The full-length PRO189 protein shown in FIG. 6 has anestimated molecular weight of about 41,871 daltons and a pI of about5.06. Clone DNA21624-1391 has been deposited with the ATCC. Regardingthe sequence, it is understood that the deposited clone contains thecorrect sequence, and the sequences provided herein are based on knownsequencing techniques.

Analyzing the amino acid sequence of SEQ ID NO:8, the putativeN-glycosylation sites are at about amino acids 224–227, 246–249 and285–288. A domain for cytosolic fatty-acid binding proteins is at aminoacids 78–107 of SEQ ID NO:8. The corresponding nucleotides can beroutinely determined given the sequences provided herein.

Some sequence identity was found to W01A6.1 and F35D11.11, C. Elegansproteins, designated in a Dayhoff database as CEW01A6_(—)10 andCELF35D11_(—)11, respectively. Some sequence identity was also found toan antigen to malaria and to restin, designated in a Dayhoff database asP_R05766 and AF014012_(—)1, respectively. Some sequence identity wasalso found to a microtubule binding protein and to myosin, designated ina Dayhoff database as AF041382_(—)1 and S07537, respectively. There isalso some sequence identity with 1-phosphatidylinositol4,5-bisphosphate, designated as PIP1_RAT.

Example 7 Isolation of cDNA Clones Encoding Human PRO190

A clone designated herein as DNA 14232 was isolated as described inExample 2 above from a human fetal retina tissue library. The DNA14232sequence is shown in FIG. 10 (SEQ ID NO:15). Based on the DNA14232sequence, oligonucleotides were synthesized: 1) to identify by PCR acDNA library that contained the sequence of interest, and 2) for use asprobes to isolate a clone of the full-length coding sequence for PRO190.Forward and reverse PCR primers generally range from 20 to 30nucleotides and are often designed to give a PCR product of about100–1000 bp in length. The probe sequences are typically 40–55 bp inlength. In order to screen several libraries for a full-length clone,DNA from the libraries was screened by PCR amplification, as per Ausubelet al., Current Protocols in Molecular Biology, with the PCR primerpair. A positive library was then used to isolate clones encoding thegene of interest using the probe oligonucleotide and one of the primerpairs.

A pair of PCR primers (forward and reverse) were synthesized:

forward PCR primer 5′-CTATACCTACTGTAGCTTCT-3′ (SEQ ID NO:16); andreverse PCR primer 5′-TCAGAGAATTCCTTCCAGGA-3′ (SEQ ID NO:17).Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the DNA14232 sequence which had the followingnucleotide sequence:Hybridization Probe

5′-ACAGTGCTGTAGTCATCCTGTAATATGCTCCTTGTCAACA-3′ (SEQ ID NO:18).

In order to screen several libraries for a source of a full-lengthclone, DNA from the libraries was screened by PCR amplification with thePCR primer pair identified above. A positive library was then used toisolate clones encoding the PRO190 gene using the probe oligonucleotideand one of the PCR primers.

RNA for construction of the cDNA libraries was isolated from humanretina tissue (LIB94). The cDNA libraries used to isolate the cDNAclones were constructed by standard methods using commercially availablereagents such as those from Invitrogen, San Diego, Calif. The cDNA wasprimed with oligo dT containing a NotI site, linked with blunt to SalIhemikinased adaptors, cleaved with NotI, sized appropriately by gelelectrophoresis, and cloned in a defined orientation into a suitablecloning vector (such as pRKB or pRKD; pRK5B is a precursor of pRK5D thatdoes not contain the SfiI site; see, Holmes et al., Science,253:1278–1280 (1991)) in the unique XhoI and NotI sites.

DNA sequencing of the clones isolated as described above gave sequenceswhich include the full-length DNA sequence for PRO190 [herein designatedas DNA23334-1392] (SEQ ID NO:13) and the derived protein sequence forPRO190.

The entire nucleotide sequence of DNA23334-1392 is shown in FIG. 8 (SEQID NO:13). Clone DNA23334-1392 contains a single open reading frame withan apparent translational initiation site at nucleotide positions193–195 and which ends at the stop codon at nucleotide positions1465–1467 (FIG. 8). The predicted polypeptide precursor is 424 aminoacids long (FIG. 9). The full-length PRO190 protein shown in FIG. 9 hasan estimated molecular weight of about 48,500 daltons and a pI of about8.65. Clone DNA23334-1392 has been deposited with the ATCC. Regardingthe sequence, it is understood that the deposited clone contains thecorrect sequence, and the sequences provided herein are based on knownsequencing techniques.

Analyzing the amino acid sequence of SEQ ID NO:14, the putativetransmembrane domains are at about amino acids 16–36, 50–74, 147–168,229–250, 271–293, 298–318 and 328–368 of SEQ ID No.14. N-glycosylationsites are at about amino acids 128–131, 204–207, 218–221 and 274–377 ofSEQ ID NO:14. The corresponding nucleotides can be routinely determinedgiven the sequences provided herein.

PRO190 has sequence identity with at least the following Dayhoffsequences designated as: CEZK896_(—)2, JC5023, GMS1_SCHPO and S44668.

Example 8 Isolation of cDNA Clones Encoding Human PRO341

A clone designated herein as DNA12920 was isolated as described inExample 2 above from a human placenta tissue library. The DNA12920sequence is shown in FIG. 13 (SEQ ID NO:21). The DNA12920 sequence wasthen compared to various EST databases including public EST databases(e.g., GenBank), and a proprietary EST database (LIFESEQ®, IncytePharmaceuticals, Palo Alto, Calif.) to identify homologous ESTsequences. The comparison was performed using the computer program BLASTor BLAST2 [Altschul et al., Methods in Enzymology, 266:460–480 (1996)].Those comparisons resulting in a BLAST score of 70 (or in some cases,90) or greater that did not encode known proteins were clustered andassembled into a consensus DNA sequence with the program “phrap” (PhilGreen, University of Washington, Seattle, Wash.). This consensussequence is herein designated DNA25314. Oligonucleotide primers basedupon the DNA25314 sequence were then synthesized and employed to screena human placenta cDNA library which resulted in the identification ofthe DNA26288-1239 clone shown in FIG. 11. The cloning vector was pRK5B(pRK5B is a precursor of pRK5D that does not contain the SfiI site; see,Holmes et al., Science, 253:1278–1280 (1991)), and the cDNA size cut wasless than 2800 bp.

A full length clone was identified that contained a single open readingframe with an apparent translational initiation site at nucleotidepositions 380–382, and a stop signal at nucleotide positions 1754–1756(FIG. 11, SEQ ID NO:19). The predicted polypeptide precursor is 458amino acids long, has a calculated molecular weight of approximately50,264 daltons and an estimated pI of approximately 8.17. Analysis ofthe full-length PRO341 sequence shown in FIG. 12 (SEQ ID NO:20)evidences the presence of the following: a signal peptide from aboutamino acid 1 to about amino acid 17, transmembrane domains from aboutamino acid 171 to about amino acid 190, from about amino acid 220 toabout amino acid 239, from about amino acid 259 to about amino acid 275,from about amino acid 286 to about amino acid 305, from about amino acid316 to about amino acid 335, from about amino acid 353 to about aminoacid 378 and from about amino acid 396 to about amino acid 417 andpotential N-glycosylation sites from about amino acid 145 to about aminoacid 147 and from about amino acid 155 to about amino acid 158. CloneDNA26288-1239 has been deposited with ATCC on Apr. 21, 1998 and isassigned ATCC deposit no. 209792.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST-2 sequence alignment analysis of the full-length sequenceshown in FIG. 12 (SEQ ID NO:20), evidenced homology between the PRO341amino acid sequence and the following Dayhoff sequences: S75696, H69788,D69852, A69888, B64918, F64752, LPU89276_(—)1, G64962, S52977 andS44253.

Example 9 Isolation of cDNA Clones Encoding Human PRO180

A clone designated herein as DNA12922 was isolated as described inExample 2 above from a human placenta tissue library. The DNA12922sequence is shown in FIG. 16 (SEQ ID NO:24). The DNA12922 sequence wasthen compared to various EST databases including public EST databases(e.g., GenBank), and a proprietary EST database (LIFESEQ®, IncytePharmaceuticals, Palo Alto, Calif.) to identify homologous ESTsequences. The comparison was performed using the computer program BLASTor BLAST2 [Altschul et al., Methods in Enzymology, 266:460–480 (1996)].Those comparisons resulting in a BLAST score of 70 (or in some cases,90) or greater that did not encode known proteins were clustered andassembled into a consensus DNA sequence with the program “phrap” (PhilGreen, University of Washington, Seattle, Wash.).

An oligonucleotide probe was formed based upon the consensus sequenceobtained above. This probe had the following sequence.

-   5′-ACCTGTTAGAAATGTGGTGGTTTCAGCAAGGCCTCAGTTT (SEQ ID NO:25).

This probe was used to screen a human placenta library prepared asdescribed in paragraph 1 of Example 2 above. The cloning vector waspRK5B (pRK5B is a precursor of pRK5D that does not contain the SfiIsite; see, Holmes et al., Science, 253:1278–1280 (1991)), and the cDNAsize cut was less than 2800 bp. A clone designated herein asDNA26843-1389 was obtained.

The entire nucleotide sequence of DNA26843-1389 is shown in FIG. 14 (SEQID NO:22). Clone DNA26843-1389 contains a single open reading frame withan apparent translational initiation site at nucleotide positions121–123 and ending at the stop codon at nucleotide positions 919–921(FIG. 14). The predicted polypeptide precursor is 266 amino acids long(FIG. 15). The full-length PRO180 protein shown in FIG. 15 has anestimated molecular weight of about 29,766 daltons and a pI of about8.39. Clone DNA26843-1389 has been deposited with the ATCC. Regardingthe sequence, it is understood that the deposited clone contains thecorrect sequence, and the sequences provided herein are based on knownsequencing techniques.

Still analyzing the amino acid sequence of SEQ ID NO:23, thetransmembrane domains are at about amino acids 13–33 (type II), 54–73,94–113, 160–180 and 122–141 of SEQ ID NO:23. N-myristoylation sites areat about amino acids 57–62, 95–100, 99–104, 124–129 and 183–188 of SEQID NO:23. The corresonding nucleotides can be routinely determined giventhe sequences provided herein.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 15 (SEQ ID NO:23), evidenced some sequence identitybetween the PRO180 amino acid sequence and the following Dayhoffsequences: CEC33A11_(—)2, CEG11E6_(—)5, CELW03A5_(—)1 AND PEU83861_(—)2(NADH dehydrogenase subunit 4L, mitochondrion).

Example 10 Isolation of cDNA Clones Encoding Human PRO194

A consensus DNA sequence was assembled relative to other EST sequencesusing phrap as described in Example 1 above. This consensus sequence isherein DNA19464. Based on the DNA19464 consensus sequence,oligonucleotides were synthesized: 1) to identify by PCR a cDNA librarythat contained the sequence of interest, and 2) for use as probes toisolate a clone of the full-length coding sequence for PRO194. PCRprimers (forward and reverse) were synthesized based upon the DNA19464sequence. Additionally, a synthetic oligonucleotide hybridization probewas constructed from the consensus DNA19464 sequence.

In order to screen several libraries for a source of a full-lengthclone, DNA from the libraries was screened by PCR amplification with thePCR primer pair identified above. A positive library was then used toisolate clones encoding the PRO194 gene using the probe oligonucleotideand one of the PCR primers. RNA for construction of the cDNA librarieswas isolated from human fetal lung tissue (LIB25).

DNA sequencing of the clones isolated as described above gave thefull-length DNA sequence for PRO194 [herein designated as DNA26844-1394](SEQ ID NO:27) and the derived protein sequence for PRO194.

The entire nucleotide sequence of DNA26844-1394 is shown in FIG. 17 (SEQID NO:27). Clone DNA26844-1394 contains a single open reading frame withan apparent translational initiation site at nucleotide positions 81–83and ending at the stop codon at nucleotide positions 873–875 (FIG. 17).The predicted polypeptide precursor is 264 amino acids long (FIG. 18).The full-length PRO194 protein shown in FIG. 18 has an estimatedmolecular weight of about 29,665 daltons and a pI of about 9.34.Analysis of the full-length PRO194 sequence shown in FIG. 18 (SEQ IDNO:28) evidences the presence of various important polypeptides domainsas shown in FIG. 18. Clone DNA26844-1394 has been deposited with ATCC onJun. 2, 1998 and is assigned ATCC deposit no. 209926.

Analysis of the amino acid sequence of the full-length PRO194polypeptide suggests that it does not exhibit significant sequencesimilarity to any known human protein. However, an analysis of theDayhoff database (version 35.45 SwissProt 35) evidenced some homologybetween the PRO194 amino acid sequence and the following Dayhoffsequences, HUMORFT_(—)1, CET07F10_(—)5, ATFCA9_(—)12, F64934,YDJX_ECOLI, ATAF00065719F29G20.19, H70002, S76980, H64934 and S76385.

Example 11 Isolation of cDNA Clones Encoding Human PRO203

A clone designated herein as DNA15618 was isolated as described inExample 2 above from a human fetal lung tissue library. The DNA15618sequence is shown in FIG. 21 (SEQ ID NO:31). Oligonucleotide probes weregenerated from the sequence of the DNA15618 molecule and were used toscreen a human fetal lung library (LIB26) prepared as described inparagraph 1 of Example 2 above. The cloning vector was pRK5B (pRk5B is aprecursor of pRk5D that does not contain the SfiI site; see, Holmes etal., Science, 253:1278–1280 (1991)), and the cDNA size cut was less than2800 bp.

A full length clone was identified that contained a single open readingframe with an apparent translational initiation site at nucleotidepositions 159–161 and ending at the stop codon found at nucleotidepositions 1200–1202 (FIG. 19; SEQ ID NO:29). The predicted polypeptideprecursor is 347 amino acids long, has a calculated molecular weight ofapproximately 39,870 daltons and an estimated pI of approximately 6.76.Analysis of the full-length PRO203 sequence shown in FIG. 20 (SEQ IDNO:30) evidences the presence of the following: a type H transmembranedomain at about amino acid 64 to about amino acid 87; possibleN-glycosylation sites at about amino acid 147 to about amino acid 150,about amino acid 155 to about amino acid 158, and about amino acid 237to about amino acid 240; sequence identity with heavy-metal-associateddomain proteins at about amino acid 23 to about amino acid 45, andsequence identity with D-isomer specific 2-hydroxyacid dehydrogenase atabout amino acid 24 to about amino acid 34. Clone DNA30862-1396 wasdeposited with the ATCC on Jun. 2, 1998, and is assigned ATCC depositno. 209920.

Analysis of the amino acid sequence of the full-length PRO203polypeptide suggests that it possesses sequence similarity to GSTATPase, thereby indicating that PRO203 may be a novel GST ATPase. Morespecifically, an analysis of the Dayhoff database (version 35.45SwissProt 35) evidenced homology between the PRO203 amino acid sequenceand the following Dayhoff sequences, AF008124_(—)1, CFRCD1GEN_(—)1, andP_R82566.

Example 12 Isolation of cDNA Clones Encoding Human PRO290

An expressed sequence tag (EST) DNA database (LIFESEQ®, IncytePharmaceuticals, Palo Alto, Calif.) was searched and an EST wasidentified that had homology to beige and FAN. An oligonucleotide probebased upon the identified EST sequence was then synthesized and used toscreen human fetal kidney cDNA libraries in an attempt to identify afull-length cDNA clone. The oligonucleotide probe had the followingsequence: 5′-TGACTGCACTACCCCGTGGCAAGCTGTTGAGCCAGCTCAGCTG 3′ (SEQ IDNO:34).

RNA for construction of cDNA libraries was isolated from human fetalkidney tissue. The cDNA libraries used to isolate the cDNA clonesencoding human PRO290 were constructed by standard methods usingcommercially available reagents such as those from Invitrogen, SanDiego, Calif. The cDNA was primed with oligo dT containing a NotI site,linked with blunt to SalI hemikinased adaptors, cleaved with NotI, sizedappropriately by gel electrophoresis, and cloned in a definedorientation into a suitable cloning vector (such as pRKB or pRKD; pRK5Bis a precursor of pRK5D that does not contain the SfiI site; see, Holmeset al., Science 253:1278–1280 (1991)) in the unique XhoI and NotI.

A cDNA clone was identified and sequenced in entirety. The entirenucleotide sequence of DNA35680-1212 is shown in FIG. 22 (SEQ ID NO:32).Clone DNA35680-1212 contains a single open reading frame with anapparent translational initiation site at nucleotide positions 293–295,and a stop codon at nucleotide positions 3302–3304 (FIG. 22; SEQ IDNO:32). The predicted polypeptide precursor is 1003 amino acids long.

It is currently believed that the PRO290 polypeptide is related to FANand/or beige. Clone DNA35680-1212 has been deposited with ATCC and isassigned ATCC deposit no. 209790. It is understood that the depositedclone has the actual correct sequence rather than the representationsprovided herein. The full-length PRO290 protein shown in FIG. 23 has anestimated molecular weight of about 112,013 daltons and a pI of about6.4.

Example 13 Isolation of cDNA Clones Encoding Human PRO874

A consensus DNA sequence designated herein as DNA36459 was identifiedusing phrap as described in Example 1 above. Based on the DNA36459consensus sequence, oligonucleotides were synthesized: 1) to identify byPCR a cDNA library that contained the sequence of interest, and 2) foruse as probes to isolate a clone of the coding sequence for PRO874.

PCR primers (forward and reverse) were synthesized:

forward PCR primer 5′-TCGTGCCCAGGGGCTGATGTGC-3′ (SEQ ID NO:37); andreverse PCR primer 5′-GTCTTTACCCAGCCCCGGGATGCG-3′ (SEQ ID NO:38).Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the consensus DNA36459 sequence which had the followingnucleotide sequence:Hybridization Probe

-   5′-GGCCTAATCCAACGTTCTGTCTTCAATCTGCAAATCTATGGGGTCCTGGG-3′ (SEQ ID    NO:39).

In order to screen several libraries for a source of a clone, DNA fromthe libraries was screened by PCR amplification with the PCR primer pairidentified above. A positive library was then used to isolate clonesencoding the PRO874 gene using the probe oligonucleotide and one of thePCR primers. RNA for construction of the cDNA libraries was isolatedfrom human fetal lung tissue (LIB25).

DNA sequencing of the clones isolated as described above gave the DNAsequence for PRO874 [herein designated as DNA40621-1440] (SEQ ID NO:35)and the derived protein sequence for PRO874.

The entire nucleotide sequence of DNA40621-1440 is shown in FIG. 24 (SEQID NO:35). Clone DNA40621-1440 contains a single open reading frameending at the stop codon at nucleotide positions 964–966 (FIG. 24). Thepredicted polypeptide encoded by DNA40621-1440 is 321 amino acids long(FIG. 25). The PRO874 protein shown in FIG. 25 has an estimatedmolecular weight of about 36,194 daltons and a pI of about 9.85.Analysis of the PRO874 sequence shown in FIG. 25 (SEQ ID NO:36)evidenced the presence of the following: a type II transmembrane domainat about amino acids 57–80; additional transmembrane domains at aboutamino acids 110–126, 215–231, and 254–274; potential N-glycosylationsites at about amino acids 16–19, 27–30, and 289–292; sequence identitywith hypothetical YBR002c family proteins at about amino acids 276–287;and sequence identity with ammonium transporter proteins at about aminoacids 204–230. Clone DNA40621-1440 was deposited with the ATCC on Jun.2, 1998, and is assigned ATCC deposit no. 209922.

Analysis of the amino acid sequence of the PRO874 polypeptide suggeststhat it is a novel multi-span transmembrane protein. However, ananalysis of the Dayhoff database (version 35.45 SwissProt 35) evidencedsequence identity between the PRO874 amino acid sequence and thefollowing Dayhoff sequences: S67049, AF054839_(—)1, S73437, S52460, andHIVU80570_(—)1.

Example 14 Isolation of cDNA Clones Encoding Human PRO710

A yeast screening assay was employed to identify cDNA clones thatencoded potential secreted proteins. Use of this yeast screening assayallowed identification of a single cDNA clone whose sequence (hereindesignated as DNA38190) is shown in FIG. 28 (SEQ ID NO:42). Based on theDNA38190 sequence shown in FIG. 28, oligonucleotides weresynthesized: 1) to identify by PCR a cDNA library that contained thesequence of interest, and 2) for use as probes to isolate a clone of thefull-length coding sequence for PRO710. In order to screen severallibraries for a full-length clone, DNA from the libraries was screenedby PCR amplification, as per Ausubel et al., Current Protocols inMolecular Biology, with the PCR primer pair. A positive library was thenused to isolate clones encoding the gene of interest using the probeoligonucleotide and one of the primer pairs.

PCR primers (forward and reverse) were synthesized:

forward PCR primer 5′-TTCCGCAAAGAGTTCTACGAGGTGG-3′ (SEQ ID NO:43)reverse PCR primer 5′-ATTGACAACATTGACTGGCCTATGGG-3′ (SEQ ID NO:44)Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the DNA38190 sequence which had the followingnucleotide sequenceHybridization Probe

-   5′-GTGGATGCTCTGTGTGCGTGCAAGATCCTTCAGGCCTTGTTCCAGTGTGA-3′ (SEQ ID    NO:45)

In order to screen several libraries for a source of a full-lengthclone, DNA from the libraries was screened by PCR amplification with thePCR primer pair identified above. A positive library was then used toisolate clones encoding the PRO710 gene using the probe oligonucleotideand one of the PCR primers.

RNA for construction of the cDNA libraries was isolated from human fetalkidney tissue (LIB227). The cDNA libraries used to isolate the cDNAclones were constructed by standard methods using commercially availablereagents such as those from Invitrogen, San Diego, Calif. The cDNA wasprimed with oligo dT containing a NotI site, linked with blunt to SalIhemikinased adaptors, cleaved with NotI, sized appropriately by gelelectrophoresis, and cloned in a defined orientation into a suitablecloning vector (such as pRKB or pRKD; pRK5B is a precursor of pRK5D thatdoes not contain the SfiI site; see, Holmes et al., Science,253:1278–1280 (1991)) in the unique XhoI and NotI sites.

A full length clone was identified that contained a single open readingframe with an apparent translational initiation site at nucleotidepositions 67–69 and ending at the stop codon found at nucleotidepositions 1765–1767 (FIG. 26, SEQ ID NO:40). The predicted polypeptideprecursor is 566 amino acids long, has a calculated molecular weight ofapproximately 65,555 daltons and an estimated pI of approximately 5.44.Analysis of the full-length PRO710 sequence shown in FIG. 27 (SEQ IDNO:41) evidences the presence of the following: a signal peptide fromabout amino acid 1 to about amino acid 32, a transmembrane domain fromabout amino acid 454 to about amino acid 476, an aminoacyl-transfer RNAsynthetase class-II signature sequence from about amino acid 6 to aboutamino acid 26 and potential N-glycosylation sites from about amino acid111 to about amino acid 114, from about amino acid 146 to about aminoacid 149 and from about amino acid 292 to about amino acid 295. CloneDNA44161-1434 has been deposited with ATCC on May 27, 1998 and isassigned ATCC deposit no. 209907.

Analysis of the amino acid sequence of the full-length PRO710polypeptide suggests that it possesses significant sequence similarityto the CDC45 protein, thereby indicating that PRO710 may be a novelCDC45 homolog. More specifically, an analysis of the Dayhoff database(version 35.45 SwissProt 35) evidenced significant homology between thePRO710 amino acid sequence and the following Dayhoff sequences,HSAJ3728_(—)1, CEF34D10_(—)1, S64939, UMU50276_(—)1, TRHY_SHEEP,CELT14E8_(—)1, RNA1_YEAST, LVU89340_(—)1, HSU80736_(—)1 andCEZK337_(—)2.

Example 15 Isolation of cDNA Clones Encoding Human PRO1151

A consensus DNA sequence was assembled relative to other EST sequencesusing phrap as described in Example 1 above. This consensus sequence isherein designated DNA40665. Based on the DNA40665 consensus sequence,oligonucleotides were synthesized: 1) to identify by PCR a cDNA librarythat contained the sequence of interest, and 2) for use as probes toisolate a clone of the full-length coding sequence for PRO1151.

PCR primers (forward and reverse) were synthesized:

forward PCR primer 5′-CCAGACGCTGCTCTTCGAAAGGGTC-3′ (SEQ ID NO:48)reverse PCR primer 5′-GGTCCCCGTAGGCCAGGTCCAGC-3′ (SEQ ID NO:49)Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the consensus DNA40665 sequence which had the followingnucleotide sequenceHybridization Probe

-   5′-CTACTTCTTCAGCCTCAATGTGCACAGCTGGAATTACAAGGAGACGTACG-3′ (SEQ ID    NO:50)

In order to screen several libraries for a source of a full-lengthclone, DNA from the libraries was screened by PCR amplification with thePCR primer pair identified above. A positive library was then used toisolate clones encoding the PRO1151 gene using the probe oligonucleotideand one of the PCR primers. RNA for construction of the cDNA librarieswas isolated from human fetal kidney tissue.

DNA sequencing of the clones isolated as described above gave thefull-length DNA sequence for PRO1151 (designated herein as DNA44694-1500[FIG. 29, SEQ ID NO:46]; and the derived protein sequence for PRO1151.

The entire nucleotide sequence of DNA44694-1500 is shown in FIG. 29 (SEQID NO:46). Clone DNA44694-1500 contains a single open reading frame withan apparent translational initiation site at nucleotide positions272–274 and ending at the stop codon at nucleotide positions 1049–1051(FIG. 29). The predicted polypeptide precursor is 259 amino acids long(FIG. 30). The full-length PRO1151 protein shown in FIG. 30 has anestimated molecular weight of about 28,770 daltons and a pI of about6.12. Analysis of the full-length PRO1151 sequence shown in FIG. 30 (SEQID NO:47) evidences the presence of the following: a signal peptide fromabout amino acid 1 to about amino acid 20, a potential N-glycosylationsite from about amino acid 72 to about amino acid 75 and amino acidsequence blocks having homology to C1q domain-containing proteins fromabout amino acid 144 to about amino acid 178, from about amino acid 78to about amino acid 111 and from about amino acid 84 to about amino acid117. Clone UNQ581 (DNA44694-1500) has been deposited with ATCC on Aug.11, 1998 and is assigned ATCC deposit no. 203114.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST-2 sequence alignment analysis of the full-length sequenceshown in FIG. 30 (SEQ ID NO:47), evidenced significant homology betweenthe PRO1151 amino acid sequence and the following Dayhoff sequences:ACR3_HUMAN, HP25_TAMAS, HUMC1QB2_(—)1, P_R99306, CA1F_HUMAN, JX0369,CA24_HUMAN, S32436, P_R28916 and CA54_HUMAN.

Example 16 Isolation of cDNA Clones Encoding Human PRO1282

A consensus DNA sequence was assembled relative to other EST sequencesusing phrap as described in Example 1 above. This consensus sequence isdesignated herein as DNA33778. Based on the DNA33778 consensus sequence,oligonucleotides were synthesized: 1) to identify by PCR a cDNA librarythat contained the sequence of interest, and 2) for use as probes toisolate a clone of the full-length coding sequence for PRO1282.

PCR primers (forward and reverse) were synthesized:

forward PCR primer 5′TCTTCAGCCGCTTGCGCAACCTC3′ (SEQ ID NO:53); andreverse PCR primer 5′TTGCTCACATCCAGCTCCTGCAGG3′ (SEQ ID NO:54).

Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the consensus DNA33778 sequence which had the followingnucleotide sequence:

Hybridization Probe

-   5′TGGATGTTGTCCAGACAACCAGCTGGAGCTGTATCCGAGGC3′ (SEQ ID NO:55).

In order to screen several libraries for a source of a full-lengthclone, DNA from the libraries was screened by PCR amplification with thePCR primer pair identified above. A positive library was then used toisolate clones encoding the PRO1282 gene using the probe oligonucleotideand one of the PCR primers. RNA for construction of the cDNA librarieswas isolated from human fetal liver.

DNA sequencing of the clones isolated as described above gave thefull-length DNA sequence for PRO1282 (designated herein as DNA45495-1550[FIG. 31, SEQ ID NO:51]; and the derived protein sequence for PRO1282.

The entire coding sequence of PRO1282 is shown in FIG. 31 (SEQ IDNO:51). Clone DNA45495-1550 contains a single open reading frame with anapparent translational initiation site at nucleotide positions 120–122,and an apparent stop codon at nucleotide positions 2139–2141 (SEQ IDNO:51). The predicted polypeptide precursor is 673 amino acids long. Thesignal peptide is at about amino acids 1–23; the transmembrane domain isat about amino acids 579–599; an EGF-like domain cysteine patternsignature starts at about amino acid 430; and leucine zipper patternsstart at about amino acids 197 and 269 of SEQ ID NO:52, see FIG. 32.Clone DNA45495-1550 has been deposited with the ATCC and is assignedATCC deposit no. 203156. The full-length PRO1282 protein shown in FIG.32 has an estimated molecular weight of about 71,655 daltons and a pI ofabout 7.8.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST-2 sequence alignment analysis of the full-length sequenceshown in FIG. 32 (SEQ ID NO:52), revealed sequence identity between thePRO1282 amino acid sequence and the following Dayhoff sequences (datafrom database incorporated by reference): AB007876_(—)1, RNPLGPV_(—)1,MUSLRRP_(—)1, ALS_PAPPA, AC004142_(—)1, ALS_HUMAN, AB014462_(—)1,DMTARTAN_(—)1, HSCHON03_(—)1 and S46224.

Example 17 Isolation of cDNA Clones Encoding Human PRO358

Using the method described in Example 1 above, a single EST sequence wasidentified in the Incyte database, designated herein as INC3115949.Based on the INC3115949 EST sequence, oligonucleotides were synthesizedto identify by PCR a cDNA library that contained the sequence ofinterest and for use as probes to isolate a clone of the full-lengthcoding sequence for PRO358.

A pair of PCR primers (forward and reverse) were synthesized:

forward PCR primer 5′-TCCCACCAGGTATCATAAACTGAA-3′ (SEQ ID NO:58) reversePCR primer 5′-TTATAGACAATCTGTTCTCATCAGAGA-3′ (SEQ ID NO:59)A probe was also synthesized:

-   5′-AAAAAGCATACTTGGAATGGCCCAAGGATAGGTGTAAATG-3′ (SEQ ID NO:60)

In order to screen several libraries for a source of a full-lengthclone, DNA from the libraries was screened by PCR amplification with thePCR primer pair identified above. A positive library was then used toisolate clones encoding the PRO358 gene using the probe oligonucleotideand one of the PCR primers. RNA for construction of the cDNA librarieswas isolated from human bone marrow (LIB256). The cDNA libraries used toisolated the cDNA clones were constructed by standard methods usingcommercially available reagents such as those from Invitrogen, SanDiego, Calif. The cDNA was primed with oligo dT containing a NotI site,linked with blunt to SalI hemikinased adaptors, cleaved with NotI, sizedappropriately by gel electrophoresis, and cloned in a definedorientation into a suitable cloning vector (such as pRKB or pRKD; pRK5Bis a precursor of pRK5D that does not contain the SfiI site; see, Holmeset al., Science, 253:1278–1280 (1991)) in the unique XhoI and NotIsites.

DNA sequencing of the clones isolated as described above gave thefull-length DNA sequence for PRO358 (FIG. 33, SEQ ID NO:56) and thederived protein sequence for PRO358 (FIGS. 34, SEQ ID NO:57).

The entire nucleotide sequence of the clone identified (DNA47361-1154)is shown in FIG. 33 (SEQ ID NO:56). Clone DNA47361-1154 contains asingle open reading frame with an apparent translational initiation site(ATG start signal) at nucleotide positions underlined in FIG. 33. Thepredicted polypeptide precursor is 811 amino acids long, including aputative signal sequence (amino acids 1 to 19), an extracellular domain(amino acids 20 to 575, including leucine rich repeats in the regionfrom position 55 to position 575), a putative transmembrane domain(amino acids 576 to 595). Clone DNA47361-1249 has been deposited withATCC and is assigned ATCC deposit no. 209431.

Example 18 Isolation of cDNA Clones Encoding Human PRO1310

A consensus DNA sequence was assembled relative to other EST sequencesusing phrap as described in Example 1 above. This consensus sequence isdesignated herein as DNA37164. Based on the DNA37164 consensus sequence,oligonucleotides were synthesized: 1) to identify by PCR a cDNA librarythat contained the sequence of interest, and 2) for use as probes toisolate a clone of the full-length coding sequence for PRO1310.

PCR primers (forward and reverse) were synthesized:

forward PCR primer: 5′GTTCTCAATGAGCTACCCGTCCCC3′ (SEQ ID NO:63) andreverse PCR primer: 5′CGCGATGTAGTGGAACTCGGGCTC3′ (SEQ ID NO:64).

Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the consensus DNA47394 sequence which had the followingnucleotide sequence:

Hybridization Probe

-   5′ ATCCGCATAAACCCTCAGTCCTGGTTTGATAATGGGAGCATCTGCATGAG3′ (SEQ ID    NO:65).

In order to screen several libraries for a source of a full-lengthclone, DNA from the libraries was screened by PCR amplification with thePCR primer pair identified above. A positive library was then used toisolate clones encoding the PRO1310 gene using the probe oligonucleotideand one of the PCR primers. RNA for construction of the cDNA librarieswas isolated from human fetal liver tissue.

DNA sequencing of the clones isolated as described above gave thefull-length DNA sequence for PRO1310 and the derived protein sequencefor PRO1310.

The entire coding sequence of PRO1310 is shown in FIG. 35 (SEQ IDNO:61). Clone DNA47394-1572 contains a single open reading frame with anapparent translational initiation site at nucleotide positions 326–328,and an apparent stop codon at nucleotide positions 2594–2596 (SEQ IDNO:61). The predicted polypeptide precursor is 765 amino acids long. Thesignal peptide is at about amino acids 1–25 of SEQ ID NO:62. CloneDNA47394-1572 has been deposited with ATCC and is assigned ATCC depositno. 203109. The full-length PRO1310 protein shown in FIG. 36 has anestimated molecular weight of about 85,898 daltons and a pI of about6.87.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST-2 sequence alignment analysis of the full-length sequenceshown in FIG. 36 (SEQ ID NO:62), revealed sequence identity between thePRO1310 amino acid sequence and the following Dayhoff sequences:AF017639_(—)1, P_W36817, JC5256, CBPH_HUMAN, MMU23184_(—)1, CBPN_HUMAN,HSU83411_(—)1, CEF01D4_(—)7, RNU62897_(—)1 and P_W11851.

Example 19 Isolation of cDNA Clones Encoding Human PRO698

A yeast screening assay was employed to identify cDNA clones thatencoded potential secreted proteins. Use of this yeast screening assayallowed identification of a single cDNA clone whose sequence (hereindesignated as DNA39906) is shown in FIG. 39 (SEQ ID NO:68). Based on theDNA39906 sequence shown in FIG. 39, oligonucleotides weresynthesized: 1) to identify by PCR a cDNA library that contained thesequence of interest, and 2) for use as probes to isolate a clone of thefull-length coding sequence for PRO698. In order to screen severallibraries for a full-length clone, DNA from the libraries was screenedby PCR amplification, as per Ausubel et al., Current Protocols inMolecular Biology, with the PCR primer pair. A positive library was thenused to isolate clones encoding the gene of interest using the probeoligonucleotide and one of the primer pairs.

PCR primers (forward and reverse) were synthesized:

forward PCR primer 5′-AGCTGTGGTCATGGTGGTGTGGTG-3′ (SEQ ID NO:69) reversePCR primer 5′-CTACCTTGGCCATAGGTGATCCGC-3′ (SEQ ID NO:70)Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the consensus DNA39906 sequence which had the followingnucleotide sequenceHybridization Probe

-   5′-CATCAGCAAACCGTCTGTGGTTCAGCTCAACTGGAGAGGGTT-3′ (SEQ ID NO:71)

In order to screen several libraries for a source of a full-lengthclone, DNA from the libraries was screened by PCR amplification with thePCR primer pair identified above. A positive library was then used toisolate clones encoding the PRO698 gene using the probe oligonucleotideand one of the PCR primers. RNA for construction of the cDNA librarieswas isolated from human bone marrow tissue (LIB255). The cDNA librariesused to isolate the cDNA clones were constructed by standard methodsusing commercially available reagents such as those from Invitrogen, SanDiego, Calif. The cDNA was primed with oligo dT containing a NotI site,linked with blunt to SalI hemikinased adaptors, cleaved with NotI, sizedappropriately by gel electrophoresis, and cloned in a definedorientation into a suitable cloning vector (such as pRKB or pRKD; pRK5Bis a precursor of pRK5D that does not contain the SfiI site; see, Holmeset al., Science, 253:1278–1280 (1991)) in the unique XhoI and NotIsites.

A full length clone was identified that contained a single open readingframe with an apparent translational initiation site at nucleotidepositions 14–16 and ending at the stop codon found at nucleotidepositions 1544–1546 (FIG. 37, SEQ ID NO:66). The predicted polypeptideprecursor is 510 amino acids long, has a calculated molecular weight ofapproximately 57,280 daltons and an estimated pI of approximately 5.61.Analysis of the full-length PRO698 sequence shown in FIG. 38 (SEQ IDNO:67) evidences the presence of the following: a signal peptide fromabout amino acid 1 to about amino acid 20, potential N-glycosylationsites from about amino acid 72 to about amino acid 75, from about aminoacid 136 to about amino acid 139, from about amino acid 193 to aboutamino acid 196, from about amino acid 253 to about amino acid 256, fromabout amino acid 352 to about amino acid 355 and from about amino acid411 to about amino acid 414 an amino acid block having homology tolegume lectin beta-chain proteins from about amino acid 20 to aboutamino acid 39 and an amino acid block having homology to the HBGF/FGFfamily of proteins from about amino acid 338 to about amino acid 365.Clone DNA48320-1433 has been deposited with ATCC on May 27, 1998 and isassigned ATCC deposit no. 209904.

Analysis of the amino acid sequence of the full-length PRO698polypeptide suggests that it possesses significant sequence similarityto the olfactomedin protein, thereby indicating that PRO698 may be anovel olfactomedin homolog. More specifically, an analysis of theDayhoff database (version 35.45 SwissProt 35) evidenced significanthomology between the PRO698 amino acid sequence and the followingDayhoff sequences, OLFM_RANCA, I73637, AB006686S3_(—)1, RNU78105_(—)1,RNU72487_(—)1, P_R98225, CELC48E7_(—)4, CEF11C3_(—)3, XLU85970_(—)1 andS42257.

Example 20 Isolation of cDNA Clones Encoding Human PRO732

A yeast screening assay was employed to identify cDNA clones thatencoded potential secreted proteins. Use of this yeast screening assayallowed identification of a single cDNA clone whose sequence (hereindesignated as DNA42580) is shown in FIG. 45 (SEQ ID NO:77). The DNA42580sequence was then compared to a variety of known EST sequences toidentify homologies. The EST databases employed included public ESTdatabases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ™,Incyte Pharmaceuticals, Palo Alto, Calif.). The search was performedusing the computer program BLAST or BLAST2 (Altshul et al., Methods inEnzymology 266:460–480 (1996)) as a comparison to a 6 frame translationof the EST sequence. Those comparisons resulting in a BLAST score of 70(or in some cases 90) or greater that did not encode known proteins wereclustered and assembled into consensus DNA sequences with the program“phrap” (Phil Green, University of Washington, Seattle, Wash.).

Using the above analysis, a consensus DNA sequence was assembledrelative to other EST sequences using phrap. This consensus sequence isherein designated consen01. Proprietary Genentech EST sequences wereemployed in the consensus assembly and they are herein designatedDNA20239 (FIG. 42; SEQ ID NO:74), DNA38050 (FIG. 43; SEQ ID NO:75) andDNA40683 (FIG. 44; SEQ ID NO:76).

Based on the consen01 sequence, oligonucleotides were synthesized: 1) toidentify by PCR a cDNA library that contained the sequence of interest,and 2) for use as probes to isolate a clone of the full-length codingsequence for PRO732. Forward and reverse PCR primers generally rangefrom 20 to 30 nucleotides and are often designed to give a PCR productof about 100–1000 bp in length. The probe sequences are typically 40–55bp in length. In some cases, additional oligonucleotides are synthesizedwhen the consensus sequence is greater than about 1–1.5 kbp. In order toscreen several libraries for a full-length clone, DNA from the librarieswas screened by PCR amplification, as per Ausubel et al., CurrentProtocols in Molecular Biology, with the PCR primer pair. A positivelibrary was then used to isolate clones encoding the gene of interestusing the probe oligonucleotide and one of the primer pairs.

PCR primers (forward and reverse) were synthesized:

forward PCR primer 5′-ATGTTTGTGTGGAAGTGCCCCG-3′ (SEQ ID NO:78) forwardPCR primer 5′-GTCAACATGCTCCTCTGC-3′ (SEQ ID NO:79) reverse PCR primer5′-AATCCATTGTGCACTGCAGCTCTAGG-3′ (SEQ ID NO:80) reverse PCR primer5′-GAGCATGCCACCACTGGACTGAC-3′ (SEQ ID NO:81)Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the consensus DNA44143 sequence which had the followingnucleotide sequenceHybridization Probe

-   5′-GCCGATGCTGTCCTAGTGGAAACAACTCCACTGTAACTAGATTGATCTATGCAC-3′ (SEQ ID    NO:82)

In order to screen several libraries for a source of a full-lengthclone, DNA from the libraries was screened by PCR amplification with thePCR primer pairs identified above. A positive library was then used toisolate clones encoding the PRO732 gene using the probe oligonucleotideand one of the PCR primers.

RNA for construction of the cDNA libraries was isolated from human fetallung tissue (LIB26). The cDNA libraries used to isolate the cDNA cloneswere constructed by standard methods using commercially availablereagents such as those from Invitrogen, San Diego, Calif. The cDNA wasprimed with oligo dT containing a NotI site, linked with blunt to SalIhemikinased adaptors, cleaved with NotI, sized appropriately by gelelectrophoresis, and cloned in a defined orientation into a suitablecloning vector (such as pRKB or pRKD; pRK5B is a precursor of pRK5D thatdoes not contain the SfiI site; see, Holmes et al., Science,253:1278–1280 (1991)) in the unique XhoI and NotI sites.

A full length clone was identified that contained a single open readingframe with an apparent translational initiation site at nucleotidepositions 88–90 and ending at the stop codon found at nucleotidepositions 1447–1449 (FIG. 40, SEQ ID NO:72). The predicted polypeptideprecursor is 453 amino acids long, has a calculated molecular weight ofapproximately 50,419 daltons and an estimated pI of approximately 5.78.Analysis of the full-length PRO732 sequence shown in FIG. 41 (SEQ IDNO:73) evidences the presence of the following: a signal peptide fromabout amino acid 1 to about amino acid 28, transmembrane domains fromabout amino acid 37 to about amino acid 57, from about amino acid 93 toabout amino acid 109, from about amino acid 126 to about amino acid 148,from about amino acid 151 to about amino acid 172, from about amino acid197 to about amino acid 215, from about amino acid 231 to about aminoacid 245, from about amino acid 260 to about amino acid 279, from aboutamino acid 315 to about amino acid 333, from about amino acid 384 toabout amino acid 403 and from about amino acid 422 to about amino acid447, potential N-glycosylation sites from about amino acid 33 to aboutamino acid 36, from about amino acid 34 to about amino acid 37, fromabout amino acid 179 to about amino acid 183, from about amino acid 298to about amino acid 301, from about amino acid 337 to about amino acid340 and from about amino acid 406 to about amino acid 409, an amino acidblock having homology to the MIP family of proteins from about aminoacid 119 to about amino acid 149 and an amino acid block having homologyto DNA/RNA non-specific endonuclease proteins from about amino acid 279to about amino acid 286. Clone DNA48334-1435 has been deposited withATCC on Jun. 2, 1998 and is assigned ATCC deposit no. 209924.

Analysis of the amino acid sequence of the full-length PRO732polypeptide suggests that it possesses significant sequence similarityto the Diff33 protein, thereby indicating that PRO732 may be a novelDiff33 homolog. More specifically, an analysis of the Dayhoff database(version 35.45 SwissProt 35) evidenced significant homology between thePRO732 amino acid sequence and the following Dayhoff sequences,HS179M20_(—)2, MUSTETU_(—)1, CER11H6_(—)2, RATDRP_(—)1, S51256, E69226,AE000869_(—)1, JC4120 CYB_PARTE and P_R50619.

Example 21 Isolation of cDNA Clones Encoding Human PRO1120

A consensus DNA sequence was assembled relative to other EST sequencesusing phrap as described in Example 1 above. This consensus sequence isdesignated herein consen0352. The consen0352 sequence was then extendedusing repeated cycles of BLAST and phrap to extend the consensussequence as far as possible using the sources of EST sequences discussedabove. The extended consensus sequence is designated herein as DNA34365.Based on the DNA34365 consensus sequence, oligonucleotides weresynthesized: 1) to identify by PCR a cDNA library that contained thesequence of interest, and 2) for use as probes to isolate a clone of thefull-length coding sequence for PRO1120.

PCR primers (forward and reverse) were synthesized:

forward PCR primers: 5′-GAAGCCGGCTGTCTGAATC-3′ (SEQ ID NO:85),5′-GGCCAGCTATCTCCGCAG-3′ (SEQ ID NO:86), 5′-AAGGGCCTGCAAGAGAAG-3′ (SEQID NO:87), 5′-CACTGGGACAACTGTGGG-3′ (SEQ ID NO:88),5′-CAGAGGCAACGTGGAGAG-3′ (SEQ ID NO:89), and 5′-AAGTATTGTCATACAGTGTTC-3′(SEQ ID NO:90); reverse PCR primers: 5′-TAGTACTTGGGCACGAGGTTGGAG-3′ (SEQID NO:91), and 5′-TCATACCAACTGCTGGTCATTGGC-3′ (SEQ ID NO:92).

Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the DNA34365 consensus sequence which had the followingnucleotide sequence:

Hybridization Probe

-   5′-CTCAAGCTGCTGGACACGGAGCGGCCGGTGAATCGGTTTCACTTG-3′ (SEQ ID NO:93).

In order to screen several libraries for a source of a full-lengthclone, DNA from the libraries was screened by PCR amplification with thePCR primer pairs identified above. A positive library was then used toisolate clones encoding the PRO1120 gene using the probe oligonucleotideand one of the PCR primers. RNA for construction of the cDNA librarieswas isolated from human fetal kidney tissue.

DNA sequencing of the clones isolated as described above gave thefull-length DNA sequence for PRO1120 (designated herein as DNA48606-1479[FIG. 46, SEQ ID NO:83]; and the derived protein sequence for PRO1120.

The entire coding sequence of PRO1120 is shown in FIG. 46 (SEQ IDNO:83). Clone DNA48606-1479 contains a single open reading frame with anapparent translational initiation site at nucleotide positions 608–610and an apparent stop codon at nucleotide positions 3209–3211. Thepredicted polypeptide precursor is 867 amino acids long. The full-lengthPRO1120 protein shown in FIG. 47 has an estimated molecular weight ofabout 100,156 Daltons and a pI of about 9.44. Additional features of thePRO1120 polypeptide include a signal peptide at about amino acids 1–17;a sulfatase signature at about amino acids 86–98; regions of homology tosulfatases at about amino acids 87–106, 133–146, 216–229, 291–320, and365–375; and potential N-glycosylation sites at about amino acids 65–68,112–115, 132–135, 149–152, 171–174, 198–201, 241–245, 561–564, 608–611,717–720, 754–757, and 764–767.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST-2 sequence alignment analysis of the full-length sequenceshown in FIG. 47 (SEQ ID NO:84), revealed significant homology betweenthe PRO1120 amino acid sequence and the following Dayhoff sequences:CELK09C4_(—)1, GL6S_HUMAN, G65169, NCU89492_(—)1, BCU44852_(—)1, E64903,P_R51355, STS_HUMAN, GA6S_HUMAN, and IDS_MOUSE. Clone DNA48606-1479 wasdeposited with the ATCC on Jul. 1, 1998, and is assigned ATCC depositno. 203040.

Example 22 Isolation of cDNA Clones Encoding Human PRO537

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of an EST cluster sequence from the Incytedatabase, designated as Incyte EST cluster no. 29605. This EST clustersequence was then compared to a variety of expressed sequence tag (EST)databases which included public EST databases (e.g., GenBank) and aproprietary EST DNA database (LIFESEQ®, Incyte Pharmaceuticals, PaloAlto, Calif.) to identify existing homologies. The homology search wasperformed using the computer program BLAST or BLAST2 (Altshul et al.,Methods in Enzymology 266:460–480 (1996)). Those comparisons resultingin a BLAST score of 70 (or in some cases 90) or greater that did notencode known proteins were clustered and assembled into a consensus DNAsequence with the program “phrap” (Phil Green, University of Washington,Seattle, Wash.). The consensus sequence obtained therefrom is hereindesignated DNA48350.

In light of an observed sequence homology between the DNA48350 consensussequence and an EST sequence encompassed within the Merck EST clone no.R63443, the Merck EST clone R63443 was purchased and the cDNA insert wasobtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.48 and is herein designated as DNA49141-1431.

Clone DNA49141-1431 contains a single open reading frame with anapparent translational initiation site at nucleotide positions 97–99 andending at the stop codon at nucleotide positions 442–444 (FIG. 48). Thepredicted polypeptide precursor is 115 amino acids long (FIG. 49). Thefull-length PRO537 protein shown in FIG. 49 has an estimated molecularweight of about 13,183 daltons and a pI of about 12.13. Analysis of thefull-length PRO537 sequence shown in FIG. 49 (SEQ ID NO:95) evidencesthe presence of the following: a signal peptide from about amino acid 1to about amino acid 31, a potential N-glycosylation site from aboutamino acid 44 to about amino acid 47, potential N-myristolation sitesfrom about amino acid 3 to about amino acid 8 and from about amino acid16 to about amino acid 21 and an amino acid block having homology tomulticopper oxidase proteins from about amino acid 97 to about aminoacid 105. Clone DNA49141-1431 has been deposited with ATCC on Jun. 23,1998 and is assigned ATCC deposit no. 203003.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST-2 sequence alignment analysis of the full-length sequenceshown in FIG. 49 (SEQ ID NO:95), evidenced homology between the PRO537amino acid sequence and the following Dayhoff sequences: A54523,CELF22H10_(—)2, FKH4_MOUSE, OTX1_HUMAN, URB1_USTMA, KNOB_PLAFN,A32895_(—)1, AF036332_(—)1, HRG_HUMAN and HRP3_PLAFS.

Example 23 Isolation of cDNA Clones Encoding Human PRO536

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of an EST cluster sequence from the Incytedatabase, designated herein as ss.clu2437.init. This EST clustersequence was then compared to a variety of expressed sequence tag (EST)databases which included public EST databases (e.g., GenBank) and aproprietary EST DNA database (LIFESEQ®, Incyte Pharmaceuticals, PaloAlto, Calif.) to identify existing homologies. The homology search wasperformed using the computer program BLAST or BLAST2 (Altshul et al.,Methods in Enzymology 266:460–480 (1996)). Those comparisons resultingin a BLAST score of 70 (or in some cases 90) or greater that did notencode known proteins were clustered and assembled into a consensus DNAsequence with the program “phrap” (Phil Green, University of Washington,Seattle, Wash.). The consensus sequence obtained therefrom is hereindesignated DNA48351.

In light of an observed sequence homology between the DNA48351 consensussequence and an EST sequence encompassed within the Merck EST clone no.H1129, the Merck EST clone H111129 was purchased and the cDNA insert wasobtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.50 and is herein designated as DNA49142-1430.

Clone DNA49142-1430 contains a single open reading frame with anapparent translational initiation site at nucleotide positions 48–50 andending at the stop codon at nucleotide positions 987–989 (FIG. 50). Thepredicted polypeptide precursor is 313 amino acids long (FIG. 51). Thefull-length PRO536 protein shown in FIG. 51 has an estimated molecularweight of about 34,189 daltons and a pI of about 4.8. Analysis of thefull-length PRO536 sequence shown in FIG. 51 (SEQ ID NO:97) evidencesthe presence of the following: a signal peptide from about amino acid 1to about amino acid 25, a potential N-glycosylation site from aboutamino acid 45 to about amino acid 48 and an amino acid sequence blockhaving homology to sulfatase proteins from about amino acid 16 to aboutamino acid 26. Clone DNA49142-1430 has been deposited with ATCC on Jun.23, 1998 and is assigned ATCC deposit no. 203002.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST-2 sequence alignment analysis of the full-length sequenceshown in FIG. 51 (SEQ ID NO:97), evidenced homology between the PRO536amino acid sequence and the following Dayhoff sequences: APU46857_(—)1,PK2_DICDI, H64743, F5I14_(—)18, CEAM_(—) ECOLI, GEN14267, H64965,TCU39815_(—)1, PSBJ_ODOSI and P_R06980.

Example 24 Isolation of cDNA Clones Encoding Human PRO535

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of an EST cluster sequence from the Incytedatabase, designated herein as ss.clu12694.init. This EST clustersequence was then compared to a variety of expressed sequence tag (EST)databases which included public EST databases (e.g., GenBank) and aproprietary EST DNA database (LIFESEQ®, Incyte Pharmaceuticals, PaloAlto, Calif.) to identify existing homologies. The homology search wasperformed using the computer program BLAST or BLAST2 (Altshul et al.,Methods in Enzymology 266:460–480 (1996)). Those comparisons resultingin a BLAST score of 70 (or in some cases 90) or greater that did notencode known proteins were clustered and assembled into a consensus DNAsequence with the program “phrap” (Phil Green, University of Washington,Seattle, Wash.). The consensus sequence obtained therefrom is hereindesignated DNA48352. Two propietary Genentech EST sequences wereemployed in the assembly are herein shown in FIGS. 54 and 55.

In light of an observed sequence homology between the DNA48352 consensussequence and an EST sequence encompassed within the Merck EST clone no.H86994, the Merck EST clone H86994 was purchased and the cDNA insert wasobtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.52 and is herein designated as DNA49143-1429.

Clone DNA49143-1429 contains a single open reading frame with anapparent translational initiation site at nucleotide positions 78–80 andending at the stop codon at nucleotide positions 681–683 (FIG. 52). Thepredicted polypeptide precursor is 201 amino acids long (FIG. 53). Thefull-length PRO535 protein shown in FIG. 53 has an estimated molecularweight of about 22,180 daltons and a pI of about 9.68. Analysis of thefull-length PRO535 sequence shown in FIG. 53 (SEQ ID NO:99) evidencesthe presence of the following: a signal peptide from about amino acid 1to about amino acid 25, a transmembrane domain from about amino acid 155to about amino acid 174, a potential N-glycosylation site from aboutamino acid 196 to about amino acid 199 and FKBP-type peptidyl-prolylcis-trans isomer signature sequences from about amino acid 62 to aboutamino acid 77, from about amino acid 87 to about amino acid 123 and fromabout amino acid 128 to about amino acid 141. Clone DNA49143-1429 hasbeen deposited with ATCC on Jun. 23, 1998 and is assigned ATCC depositno. 203013.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST-sequence alignment analysis of the full-length sequence shownin FIG. 53 (SEQ ID NO:99), evidenced homology between the PRO535 aminoacid sequence and the following Dayhoff sequences: S71237, P_R93551,P_R28980, S71238, FKB2_HUMAN, CELC05C8_(—)1, S55383, S72485,CELC50F2_(—)6 and S75144.

Example 25 Isolation of cDNA Clones Encoding Human PRO718

A cDNA sequence isolated in the amylase screen described in Example 2human fetal lung library) above is herein designated DNA43512 (see FIG.62; SEQ ID NO:108). The DNA43512 sequence was then compared to a varietyof expressed sequence tag (EST) databases which included public ESTdatabases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ™,Incyte Pharmaceuticals, Palo Alto, Calif.) to identify existinghomologies. The homology search was performed using the computer programBLAST or BLAST2 (Altshul et al., Methods in Enzymology 266:460–480(1996)). Those comparisons resulting in a BLAST score of 70 (or in somecases 90) or greater that did not encode known proteins were clusteredand assembled into consensus DNA sequences with the program “phrap”(Phil Green, University of Washington, Seattle, Wash.). The consensussequence obtained therefrom is herein designated DNA45625. ProprietaryGenentech EST sequences were employed in the assembly and are hereinshown in FIGS. 58–61.

Based on the DNA45625 sequence, oligonucleotide probes were generatedand used to screen a human fetal lung library (LIB25) prepared asdescribed in paragraph 1 of Example 2 above. The cloning vector waspRK5B (pRK5B is a precursor of pRK5D that does not contain the SfiIsite; see, Holmes et al., Science, 253:1278–1280 (1991)), and the cDNAsize cut was less than 2800 bp.

PCR primers (forward and reverse) were synthesized:

forward PCR primer 5′-GGGTGGATGGTACTGCTGCATCC-3′ (SEQ ID NO:109) reversePCR primer 5′-TGTTGTGCTGTGGGAAATCAGATGTG-3′ (SEQ ID NO:110)Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the DNA45625 sequence which had the followingnucleotide sequence:Hybridization Probe

-   5′-GTGTCTGGAGGCTGTGGCCGTTTTGTTTTCTTGGGCTAAAATCGGG-3′ (SEQ ID NO:111)

In order to screen several libraries for a source of a full-lengthclone, DNA from the libraries was screened by PCR amplification with thePCR primer pair identified above. A positive library was then used toisolate clones encoding the PRO718 gene using the probe oligonucleotideand one of the PCR primers.

A full length clone was identified that contained a single open readingframe with an apparent translational initiation site at nucleotidepositions 36–38 and ending at the stop codon found at nucleotidepositions 607–609 (FIG. 56; SEQ ID NO:102). The predicted polypeptideprecursor is 157 amino acids long, has a calculated molecular weight ofapproximately 17,400 daltons and an estimated pI of approximately 5.78.Analysis of the full-length PRO718 sequence shown in FIG. 57 (SEQ IDNO:103) evidences the presence of the following: a type II transmembranedomain from about amino acid 21 to about amino acid 40, and othertransmembrane domains at about amino acid 58 to about amino acid 78,about amino acid 95 to about amino acid 114, and about amino acid 127 toabout amino acid 147; a cell attachment sequence from about amino acid79 to about amino acid 81; and a potential N-glycosylation site fromabout amino acid 53 to about amino acid 56. Clone DNA49647-1398 has beendeposited with ATCC on Jun. 2, 1998 and is assigned ATCC deposit no.209919.

Analysis of the amino acid sequence of the full-length PRO718polypeptide suggests that it possesses no significant sequencesimilarity to any known protein. However, an analysis of the Dayhoffdatabase (version 35.45 SwissProt 35) evidenced some degree of homologybetween the PRO718 amino acid sequence and the following Dayhoffsequences: AF045606_(—)1, AF039906_(—)1, SPBC8D2_(—)2, S63441, F64728,COX1_TRYBB, F64375, E64173, RPYGJT_(—)3, MTCY261_(—)23.

Example 26 Isolation of cDNA Clones Encoding Human PRO872

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single Incyte EST sequence designated hereinas clu120709.init. The clu120709.init sequence was then compared aproprietary EST DNA database (LIFESEQ™, Incyte Pharmaceuticals, PaloAlto, Calif.) to identify existing homologies. The homology search wasperformed using the computer program BLAST or BLAST2 (Altshul et al.,Methods in Enzymology 266:460–480 (1996)). Those comparisons resultingin a BLAST score of 70 (or in some cases 90) or greater that did notencode known proteins were clustered and assembled into a consensus DNAsequence with the program “phrap” (Phil Green, University of Washington,Seattle, Wash.). The consensus sequence obtained therefrom is hereindesignated DNA48254.

In light of an observed sequence homology between the DNA48254 consensussequence and an EST sequence encompassed within the Incyte EST clone no.3438068, the Incyte EST clone 3438068 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.63 and is the full-length DNA sequence for PRO872. Clone DNA49819-1439was deposited with the ATCC on Jun. 2, 1998, and is assigned ATCCdeposit no. 209931.

The entire nucleotide sequence of DNA49819-1439 is shown in FIG. 63 (SEQID NO:112). Clone DNA49819-1439 contains a single open reading framewith an apparent translational initiation site at nucleotide positions14–16 and ending at the stop codon at nucleotide positions 1844–1846(FIG. 63). The predicted polypeptide precursor is 610 amino acids long(FIG. 64). The full-length PRO872 protein shown in FIG. 64 has anestimated molecular weight of about 66,820 daltons and a pI of about8.65. Analysis of the full-length PRO872 sequence shown in FIG. 64 (SEQID NO:113) evidences the presence of the following features: a signalpeptide at amino acid 1 to about 18, putative transmembrane domains atabout amino acids 70–87, 200–222 and 568–588; sequence identity withbacterial-type phytoene dehydrogenase protein at about amino acids71–105; sequence identity with a regulator of chromosome condensation(RCC1) signature 2 at about amino acids 201–211; leucine zipper patternsat about amino acids 214–235, 221–242, 228–249 and 364–385; a potentialN-glycosylation site at about amino acids 271–274; and aglycosaminoglycan attachment site at about amino acids 75–78. Analysisof the amino acid sequence of the full-length PRO872 polypeptide usingthe Dayhoff database (version 35.45 SwissProt 35) evidenced homologybetween the PRO872 amino acid sequence and the following Dayhoffsequences: PRCRTI_(—)1, S75951, S74689, CELF37C4_(—)3, CRTI_RHOCA,S76617, YNI2_METTL, MTV014_(—)14, AOFB_HUMAN, and MMU70429_(—)1.

Example 27 Isolation of cDNA Clones Encoding Human PRO1063

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single Incyte EST cluster sequencedesignated herein as ss.clu119743.init. The Incyte EST cluster sequencess.clu119743.init sequence was then compared to a variety of expressedsequence tag (EST) databases which included public EST databases (e.g.,GenBank) and a proprietary EST DNA database (LIFESEQ™, IncytePharmaceuticals, Palo Alto, Calif.) to identify existing homologies. Thehomology search was performed using the computer program BLAST or BLAST2(Altshul et al., Methods in Enzymology 266:460–480 (1996)). Thosecomparisons resulting in a BLAST score of 70 (or in some cases 90) orgreater that did not encode known proteins were clustered and assembledinto a consensus DNA sequence with the program “phrap” (Phil Green,University of Washington, Seattle, Wash.). The consensus sequenceobtained therefrom is herein designated DNA48288.

In light of an observed sequence homology between the DNA48288 consensussequence and an EST sequence encompassed within the Incyte EST clone no.2783726, the Incyte EST clone 2783726 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.65 and is herein designated DNA49820-1427.

The full length clone shown in FIG. 65 contained a single open readingframe with an apparent translational initiation site at nucleotidepositions 90–92 and ending at the stop codon found at nucleotidepositions 993–995 (FIG. 65; SEQ ID NO:114). The predicted polypeptideprecursor is 301 amino acids long, has a calculated molecular weight ofapproximately 33,530 daltons and an estimated pI of approximately 4.80.Analysis of the full-length PRO1063 sequence shown in FIG. 66 (SEQ IDNO:115) evidences the presence of the following: a signal peptide fromabout amino acid 1 to about amino acid 21, potential N-glycosylationsites from about amino acid 195 to about amino acid 198, from aboutamino acid 217 to about amino acid 220 and from about amino acid 272 toabout amino acid 275, a glycosaminoglycan attachment site from aboutamino acid 267 to about amino acid 270, a microbodies C-terminaltargeting signal site from about amino acid 299 to about amino acid 301,a type II fibronectin collagen-binding domain homology sequence fromabout amino acid 127 to about amino acid 168 and a fructose-bisphosphatealdolase class II protein homology sequence from about amino acid 101 toabout amino acid 118. Clone DNA49820-1427 has been deposited with theATCC on Jun. 2, 1998 and is assigned ATCC deposit no. 209932.

Analysis of the amino acid sequence of the full-length PRO1063polypeptide suggests that it possesses sequence similarity to the humantype IV collagenase protein. More specifically, an analysis of theDayhoff database (version 35.45 SwissProt 35) evidenced some degree ofhomology between the PRO1063 amino acid sequence and the followingDayhoff sequences, S68303, CFU68533_(—)1, P_P91139, RNU65656_(—)1,PA2R_RABIT, MMU56734_(—)1, FINC_XENLA, A48925, P_R92778 and FA12_HUMAN.

Example 28 Isolation of cDNA Clones Encoding Human PRO619

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of an EST cluster sequence from the Incytedatabase, designated herein as 88434. This EST cluster sequence was thencompared to a variety of expressed sequence tag (EST) databases whichincluded public EST databases (e.g., GenBank) and a proprietary EST DNAdatabase (LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, Calif.) toidentify existing homologies. The homology search was performed usingthe computer program BLAST or BLAST2 (Altshul et al., Methods inEnzymology 266:460–480 (1996)). Those comparisons resulting in a BLASTscore of 70 (or in some cases 90) or greater that did not encode knownproteins were clustered and assembled into a consensus DNA sequence withthe program “phrap” (Phil Green, University of Washington, Seattle,Wash.).

In light of an observed sequence homology between the consensus sequenceand an EST sequence encompassed within the Incyte EST clone no. 1656694,the Incyte EST clone 1656694 was purchased and the cDNA insert wasobtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.67 and is herein designated as DNA49821-1562.

The full length clone shown in FIG. 67 contained a single open readingframe with an apparent translational initiation site at nucleotidepositions 81–83 and ending at the stop codon found at nucleotidepositions 450–452 (FIG. 67; SEQ ID NO:116). The predicted polypeptideprecursor (FIG. 68, SEQ ID NO:117) is 123 amino acids long including apredicted signal peptide at about amino acids 1–20. PRO619 has acalculated molecular weight of approximately 13,710 daltons and anestimated pI of approximately 5.19. Clone DNA49821-1562 was depositedwith the ATCC on Jun. 16, 1998 and is assigned ATCC deposit no. 209981.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST-2 sequence alignment analysis of the full-length sequenceshown in FIG. 68 (SEQ ID NO:117), revealed significant homology betweenthe PRO619 amino acid sequence and the following Dayhoff sequences:S35302, D87009_(—)1, HSU93494_(—)1, HUMIGLAM5_(—)1, D86999_(—)2,HUMIGLYM1_(—)1, HUMIGLYMKE_(—)1, A29491_(—)1, A29498_(—)1, andVPR2_MOUSE.

Example 29 Isolation of cDNA Clones Encoding Human PRO943

A consensus DNA sequence encoding PRO943 was assembled relative to otherEST sequences using phrap as described in Example 1 above. Thisconsensus sequence was then extended using repeated cycles of BLAST andphrap to extend the consensus sequence as far as possible using thesources of EST sequences discussed above. The extended consensussequence is herein designated DNA36360. Based on the DNA36360 consensussequence, oligonucleotides were synthesized: 1) to identify by PCR acDNA library that contained the sequence of interest, and 2) for use asprobes to isolate a clone of the full-length coding sequence for PRO943.

PCR primers (forward and reverse) were synthesized:

forward PCR primer 5′-CGAGATGACGCCGAGCCCCC-3′ (SEQ ID NO:120) reversePCR primer 5′-CGGTTCGACACGCGGCAGGTG-3′ (SEQ ID NO:121)Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the consensus DNA36360 sequence which had the followingnucleotide sequenceHybridization Probe

-   5′-TGCTGCTCCTGCTGCCGCCGCTGCTGCTGGGGGCCTTCCCGCCGG-3′ (SEQ ID NO:122)

In order to screen several libraries for a source of a full-lengthclone, DNA from the libraries was screened by PCR amplification with thePCR primer pair identified above. A positive library was then used toisolate clones encoding the PRO943 gene using the probe oligonucleotideand one of the PCR primers. RNA for construction of the cDNA librarieswas isolated from human fetal brain tissue.

DNA sequencing of the clones isolated as described above gave thefull-length DNA sequence for PRO943 (designated herein as DNA52192-1369[FIG. 69, SEQ ID NO:118]) and the derived protein sequence for PRO943.

The entire nucleotide sequence of DNA52192-1369 is shown in FIG. 69 (SEQID NO:118). Clone DNA52192-1369 contains a single open reading framewith an apparent translational initiation site at nucleotide positions150–152 and ending at the stop codon at nucleotide positions 1662–1664(FIG. 69). The predicted polypeptide precursor is 504 amino acids long(FIG. 70). The full-length PRO943 protein shown in FIG. 70 has anestimated molecular weight of about 54,537 daltons and a pI of about10.04. Analysis of the full-length PRO943 sequence shown in FIG. 70 (SEQID NO:119) evidences the presence of the following: a signal peptidefrom about amino acid 1 to about amino acid 17, a transmembrane domainfrom about amino acid 376 to about amino acid 396, tyrosine kinasephosphorylation sites from about amino acid 212 to about amino acid 219and from about amino acid 329 to about amino acid 336, potentialN-glycosylation sites from about amino acid 111 to about amino acid 114,from about amino acid 231 to about amino acid 234, from about amino acid255 to about amino acid 258 and from about amino acid 293 to about aminoacid 296 and an immunoglobulin and MHC protein sequence homology blockfrom about amino acid 219 to about amino acid 236. Clone DNA52192-1369has been deposited with ATCC on Jul. 1, 1998 and is assigned ATCCdeposit no. 203042.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST-2 sequence alignment analysis of the full-length sequenceshown in FIG. 70 (SEQ ID NO:119), evidenced significant homology betweenthe PRO943 amino acid sequence and the following Dayhoff sequences:B49151, A39752, FGR1_XENLA, S38579, RATHBFGFRB_(—)1, TVHU2F, FGR2_MOUSE,CEK3_CHICK, P_R21080 and A27171_(—)1.

Example 30 Isolation of cDNA Clones Encoding Human PRO1188

A consensus DNA sequence was assembled relative to other EST sequencesusing the program “phrap” as described in Example 1 above. Thisconsensus sequence is designated herein as DNA45679. Based on theDNA45679 consensus sequence, oligonucleotides were synthesized: 1) toidentify by PCR a cDNA library that contained the sequence of interest,and 2) for use as probes to isolate a clone of the full-length codingsequence for PRO1188.

PCR primers (forward and reverse) were synthesized:

forward PCR primer 5′-CTGGTGCCTCAACAGGGAGCAG-3′ (SEQ ID NO:125) reversePCR primer 5′-CCATTGTGCAGGTCAGGTCACAG-3′ (SEQ ID NO:126)

Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the consensus DNA45679 sequence which had the followingnucleotide sequence:

Hybridization Probe

-   5′-CTGGAGCAAGTGCTCAGCTGCCTGTGGTCAGACTGGGGTC-3′ (SEQ ID NO:127)

In order to screen several libraries for a source of a full-lengthclone, DNA from the libraries was screened by PCR amplification with thePCR primer pair identified above. A positive library was then used toisolate clones encoding the PRO1188 gene using the probe oligonucleotideand one of the PCR primers. RNA for construction of the cDNA librarieswas isolated from human fetal kidney tissue.

DNA sequencing of the clones isolated as described above gave thefull-length DNA sequence for PRO1188 (designated herein as DNA52598-1518[FIG. 71, SEQ ID NO:123]); and the derived protein sequence for PRO1188.

The entire coding sequence of PRO1188 is shown in FIG. 71 (SEQ IDNO:123). Clone DNA52598-1518 contains a single open reading frame withan apparent translational initiation site at nucleotide positions136–138 and an apparent stop codon at nucleotide positions 3688–3690.The predicted polypeptide precursor is 1184 amino acids long. Thefull-length PRO1188 protein shown in FIG. 72 has an estimated molecularweight of about 132,582 Daltons and a pI of about 8.80. Additionalfeatures include: a signal peptide at about amino acids 1–31; an ATP/GTPbinding site motif A (P-loop) at about amino acids 266–273; an aldehydedehydrogenases cysteine active site at about amino acids 188–199; growthfactor and cytokines receptors family signature 2 at about amino acids153–159; and potential N-glycosylation sites at about amino acids129–132, 132–135, 346–349, 420–423, 550–553, 631–634, 1000–1003, and1056–1059.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST-2 sequence alignment analysis of the full-length sequenceshown in FIG. 72 (SEQ ID NO:124), revealed significant homology betweenthe PRO188 amino acid sequence and the following Dayhoff sequences:SSU83114_(—)1, S56015, CET21B6_(—)4, CELT19D2_(—)1, and TSP1_MOUSE.

Clone DNA52598-1518 has been deposited with ATCC and is assigned ATCCdeposit no 203107.

Example 31 Isolation of cDNA Clones Encoding Human PRO1133

A consensus DNA sequence was assembled relative to other EST sequencesusing phrap as described in Example 1 above. This sequence was extendedusing repeated cycles of phrap. The extended consensus sequence isdesignated herein DNA38102. Based on the DNA38102 consensus sequence,oligonucleotides were synthesized: 1) to identify by PCR a cDNA librarythat contained the sequence of interest, and 2) for use as probes toisolate a clone of the full-length coding sequence for PRO1133.

PCR primers (two forward and one reverse) were synthesized:

forward PCR primer 1 5′-TCGATTATGGACGAACATGGCAGC-3′ (SEQ ID NO:130);forward PCR primer 2 5′-TTCTGAGATCCCTCATCCTC-3′ (SEQ ID NO:131); andreverse primer 5′-AGGTTCAGGGACAGCAAGTTTGGG-3′ (SEQ ID NO:132).

Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the consensus DNA38102 sequence which had the followingnucleotide sequence:

Hybridization Probe

-   5′TTTGCTGGACCTCGGCTACGGAATTGGCTTCCCTCTACGGACAGCTGGAT3′ (SEQ ID    NO:133).

In order to screen several libraries for a source of a full-lengthclone, DNA from the libraries was screened by PCR amplification with aPCR primer pair identified above. A positive library was then used toisolate clones encoding the PRO1133 gene using the probe oligonucleotideand one of the PCR primers. RNA for construction of the cDNA librarieswas isolated from human fetal kidney tissue.

DNA sequencing of the clones isolated as described above gave thefull-length DNA sequence for PRO1133 and the derived protein sequencefor PRO1133.

The entire coding sequence of PRO1133 is shown in FIG. 73 (SEQ IDNO:128). Clone DNA53913-1490 contains a single open reading frame withan apparent translational initiation site at nucleotide positions266–268 and an apparent stop codon at nucleotide positions 1580–1582 ofSEQ ID NO:128. The predicted polypeptide precursor is 438 amino acidslong. The signal peptide is at amino acids 1–18 of SEQ ID NO:129.EGF-like domain cysteine pattern signatures start at 315 and 385 of SEQID NO:129 as shown in FIG. 74. Clone DNA53913-1490 has been depositedwith ATCC and is assigned ATCC deposit no. 203162. The full-lengthPRO1133 protein shown in FIG. 74 has an estimated molecular weight ofabout 49,260 daltons and a pI of about 6.15.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST-2 sequence alignment analysis of the full-length sequenceshown in FIG. 74 (SEQ ID NO:129), revealed some sequence identitybetween the PRO1133 amino acid sequence and the following Dayhoffsequences (data from the database incorporated herein): AF002717_(—)1,LMG1_HUMAN, B54665, UNC6_CAEEL, LML1_CAEEL, LMA5_MOUSE, MMU88353_(—)1,LMA1_HUMAN, HSLN2C64_(—)1 and AF005258_(—)1.

Example 32 Isolation of cDNA Clones Encoding Human PRO784

An initial DNA sequence (SEQ ID NO:136), referred to herein as DNA44661and shown in FIG. 77, was identified using a yeast screen, in a humanfetal lung cDNA library that preferentially represents the 5′ ends ofthe primary cDNA clones. DNA44661 was then compared to ESTs from publicdatabases (e.g., GenBank), and a proprietary EST database (LIFESEQ®,Incyte Pharmaceuticals, Palo Alto, Calif.), using the computer programBLAST or BLAST2 [Altschul et al., Methods in Enzymology, 266:460–480(1996)]. The ESTs were then clustered and assembled into a consensus DNAsequence using the computer program “phrap” (Phil Green, University ofWashington, Seattle, Wash.). The consensus sequence obtained isdesignated herein as “DNA45463”. Based on the DNA45463 consensussequence, oligonucleotides were synthesized for use as probes to isolatea clone of the full-length coding sequence for PRO784 from a human fetallung cDNA library.

The full length DNA53978-1443 clone shown in FIG. 75 contained a singleopen reading frame with an apparent translational initiation site atnucleotide positions 37–39 and ending at the stop codon found atnucleotide positions 821–823 (FIG. 75; SEQ ID NO:134). The predictedpolypeptide precursor (FIG. 76, SEQ ID NO:135) is 228 amino acids long.PRO784 has a calculated molecular weight of approximately 25,735 Daltonsand an estimated pI of approximately 5.45. PRO784 has the followingfeatures: a signal peptide at about amino acid 1 to about 15;transmembrane domains at about amino acids 68 to about 87 and at about183 to about 204; potential N-myristoylation sites at about amino acids15–20, 51–56, 66–60, 163–168, and 206–211; and an RNP-1 proteinRNA-binding region at about amino acids 108 to about 117.

Clone DNA53978-1443 was deposited with ATCC on Jun. 16, 1998, and isassigned ATCC deposit no. 209983.

Based on a BLAST and FastA sequence alignment analysis (using the ALIGNcomputer program) of the full-length sequence, PRO784 shows amino acidsequence identity to the following proteins: RNU42209_(—)1,MMU91538_(—)1, CGU91742_(—)1, CELF55A4_(—)6, SC22_YEAST, and F48188.

Example 33 Isolation of cDNA Clones Encoding Human PRO783

A yeast screening assay was employed to identify cDNA clones thatencoded potential secreted proteins. Use of this yeast screening assayallowed identification of a single cDNA clone, designated herein asDNA45201 (FIG. 80; SEQ ID NO:139).

The DNA45201 sequence was then used to search expressed sequence tag(EST) databases for the presence of potential homologies. The ESTdatabases included public EST databases (e.g., GenBank) and aproprietary EST DNA database (LIFESEQ™, Incyte Pharmaceuticals, PaloAlto, Calif.). The search was performed using the computer program BLASTor BLAST2 (Altshul et al., Methods in Enzymology 266:460–480 (1996)).Those comparisons resulting in a BLAST score of 70 (or in some cases 90)or greater that did not encode known proteins were clustered andassembled into a consensus DNA sequence with the program “phrap” (PhilGreen, Univ. of Washington, Seattle, Wash.). The consensus sequenceobtained is herein designated as “consen01”. A proprietary Genentech ESTsequence was used in the consensus assembly and is herein designated asDNA14575 (FIG. 81; SEQ ID NO:140).

Based on the consent01 sequence, oligonucleotides were synthesized: 1)to identify by PCR a cDNA library that contained the sequence ofinterest, and 2) for use as probes to isolate a clone of the full-lengthcoding sequence for PRO783. In order to screen several libraries for afull-length clone, DNA from the libraries was screened by PCRamplification, as per Ausubel et al., Current Protocols in MolecularBiology, with the PCR primer pair. A positive library was then used toisolate clones encoding the gene of interest using the probeoligonucleotide and one of the primer pairs.

PCR primers (forward and reverse) were synthesized:

forward PCR primer 5′-GACTGTATCTGAGCCCCAGACTGC-3′ (SEQ ID NO:141),forward PCR primer 5′-TCAGCAATGAGGTGCTGCTC-3′ (SEQ ID NO:142), andreverse PCR primer 5′-TGAGGAAGATGAGGGACAGGTTGG-3′ (SEQ ID NO:143).

Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the consent01sequence which had the followingnucleotide sequence:

Hybridization Probe

-   5′-TATGGAAGCACCTGACTACGAAGTGCTATCCGTGCGAGAACAGCTATTCC-3′ (SEQ ID    NO:144).

In order to screen several libraries for a source of a full-lengthclone, DNA from the libraries was screened by PCR amplification with aPCR primer pair identified above. A positive library was then used toisolate clones encoding the PRO783 gene using the probe oligonucleotideand one of the PCR primers.

RNA for construction of the cDNA libraries was isolated from human fetalkidney tissue (LIB228). The cDNA libraries used to isolate the cDNAclones were constructed by standard methods using commercially availablereagents such as those from Invitrogen, San Diego, Calif. The cDNA wasprimed with oligo dT containing a NotI site, linked with blunt to SalIhemikinased adaptors, cleaved with NotI, sized appropriately by gelelectrophoresis, and cloned in a defined orientation into a suitablecloning vector (such as pRKB or pRKD; pRK5B is a precursor of pRK5D thatdoes not contain the SfiI site; see, Holmes et al., Science,253:1278–1280 (1991)) in the unique XhoI and NotI sites.

DNA sequencing of the clones isolated as described above gave thefull-length DNA sequence for PRO783 [herein designated as DNA53996-1442](SEQ ID NO:137) and the derived protein sequence for PRO783.

The entire nucleotide sequence of DNA53996-1442 is shown in FIG. 78 (SEQID NO:137). Clone DNA53996-1442 contains a single open reading framewith an apparent translational initiation site at nucleotide positions310–312 and ending at the stop codon at nucleotide positions 1777–1779(FIG. 78). The predicted polypeptide precursor is 489 amino acids long(FIG. 79). The full-length PRO783 protein shown in FIG. 79 has anestimated molecular weight of about 55,219 daltons and a pI of about8.47. Analysis of the full-length PRO783 sequence shown in FIG. 79 (SEQID NO:138) evidences the presence of the following features:transmembrane domains located at about amino acids 23–42, 67–89,111–135, 154–176, 194–218, 296–319, 348–370, 387–410 and 427–452;leucine zipper patterns located at about amino acids 263–283 and399–420; a potential tyrosine kinase phosphorylation site at about aminoacids 180–187; potential N-glycosylation sites at about amino acids105–108 and 121–124; potential cAMP- and a cGMP-dependent protein kinasephosphorylation site at about amino acids 288–291; and a region havingsequence identity with bacterial rhodopsins retinal binding site proteinat about amino acids 190–218.

An analysis of the Dayhoff database (version 35.45 SwissProt 35) showssome sequence identity between the PRO783 amino acid sequence and thefollowing Dayhoff sequences: YNC2_CAEEL, D64048, ATAC002332_(—)3F4P9.3,NY2R_SHEEP, and VSH_MUMPA.

Clone DNA53996-1442 was deposited with the ATCC on Jun. 2, 1998, and isassigned ATCC deposit no. 209921.

Example 34 Isolation of cDNA Clones Encoding Human PRO820

An expressed sequence tag (EST) DNA database (Merck/Wash. U) wassearched and an EST designated EST no. AA504080, Merck clone 825136, wasidentified (library 312, human B-cell tonsil). Homology searchesrevealed that this EST showed sequence identity with low affinityimmunoglobulin gamma Fc receptor II. DNA sequencing gave the full-lengthDNA sequence for PRO820 and the derived protein sequence for PRO820.

The entire nucleotide sequence of DNA56041-1416 is shown in FIG. 82 (SEQID NO:145). Clone DNA56041-1416 contains a single open reading framewith an apparent translational initiation site at nucleotide positions115–117 and ending at the stop codon at nucleotide positions 487–489(FIG. 82). The predicted polypeptide precursor is 124 amino acids long(FIG. 83). The full-length PRO820 protein shown in FIG. 83 has anestimated molecular weight of about 14,080 daltons and a pI of about7.48. Clone DNA56041-1416 has been deposited with ATCC. Regarding thesequence, it is understood that the deposited clone contains the correctsequence, and the sequences provided herein are based on knownsequencing techniques.

Still analyzing the amino acid sequence of SEQ ID NO:146, the putativesignal peptide is at about amino acids 1–15 of SEQ ID NO:146. Proteinkinase C phosphorylation sites are at about amino acids 20–22 and 43–45of SEQ ID NO:146. An N-myristoylation site is at about amino acids 89–94of SEQ ID NO:146. An immunoglobulin and major histocompatibility complexdomain is at about amino acids 83–90 of SEQ ID NO:146. The correspondingnucleotides can be routinely determined given the sequences providedherein.

Example 35 Isolation of cDNA Clones Encoding Human PRO1080

A consensus DNA sequence was assembled relative to other EST sequencesusing phrap and was extended using repeated cycles of BLAST and phrap soas to extend the consensus sequence as far as possible using the sourcesof the EST sequences as described in Example 1 above. The consensussequence is designated herein as DNA52640. An EST proprietary toGenentech was employed in the consensus assembly and is hereindesignated as DNA36527 (FIG. 86; SEQ ID NO:149).

In light of an observed sequence homology between the DNA36527 consensussequence and an EST sequence encompassed within the Merck EST clone no.526423, the Merck EST clone 526423 was purchased and the cDNA insert wasobtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.84 and is herein designated as DNA56047-1456.

The entire nucleotide sequence of DNA56047-1456 is shown in FIG. 84 (SEQID NO:147). Clone DNA56047-1456 contains a single open reading framewith an apparent translational initiation site at nucleotide positions159–161 and ending at the stop codon at nucleotide positions 1233–1235of SEQ ID NO:147 (FIG. 84). The predicted polypeptide precursor is 358amino acids long (FIG. 85). The full-length PRO1080 protein shown inFIG. 85 has an estimated molecular weight of about 40,514 daltons and apI of about 6.08. Clone DNA56047-1456 has been deposited with ATCC onJun. 9, 1998. It is understood that the deposited clone has the actualnucleic acid sequence and that the sequences provided herein are basedon known sequencing techniques.

Also shown in FIG. 85 are the approximate locations of the signalpeptide, cell attachment site, Nt-DnaJ domain signature, region havingsequence identity with Nt-DnaJ domain proteins, and N-glycosylationsites. The corresponding nucleic acids of these amino acid sequences andothers provided herein can be routinely determined by the informationprovided herein.

Example 36 Isolation of cDNA Clones Encoding Human PRO1079

A consensus DNA sequence was assembled relative to other EST sequencesusing phrap as described in Example 1 above, and is herein designatedDNA52714. Based on information provided by the assembly, the clone forMerck EST no. HO6898 was obtained and sequenced, thereby giving thenucleotide sequence designated herein as DNA56050-1455. The entirenucleotide sequence of DNA56050-1455 is shown in FIG. 87 (SEQ IDNO:150). Clone DNA56050-1455 contains a single open reading frame withan apparent translational initiation site at nucleotide positions183–185 and ending at the stop codon at nucleotide positions 861–863(FIG. 87). The predicted polypeptide precursor is 226 amino acids long(FIG. 88). The full-length PRO1079 protein shown in FIG. 88 has anestimated molecular weight of about 24,611 Daltons and a pI of about4.85. Analysis of the full-length PRO1079 sequence shown in FIG. 88 (SEQID NO:3) evidences the presence of the following features: a signalpeptide at about amino acid 1–29; potential N-myristoylation sites atabout amino acids 10–15, and 51–56; homology to photosystem I psaG andpsaK proteins at about amino acids 2 to 20; and homology to prolylendopeptidase family serine proteins at about amino acids 150 to 163.

Analysis of the amino acid sequence of the full-length PRO1079polypeptide using the Dayhoff database (version 35.45 SwissProt 35)evidenced some sequence identity between the PRO1079 amino acid sequenceand the following Dayhoff sequences: CEK10C3_(—)4, MMU50734_(—)1,D69503, AF051149_(—)1, and VSMP_CVMS.

Clone UNQ536 (DNA56050-1455) was deposited with the ATCC on Jun. 22,1998, and is assigned ATCC deposit no. 203011.

Example 37 Isolation of cDNA Clones Encoding Human PRO793

A cDNA clone (DNA56110-1437) encoding a native human PRO793 polypeptidewas identified by a yeast screen, in a human skin tumor cDNA librarythat preferentially represents the 5′ ends of the primary cDNA clones.The yeast screen employed identified a single EST clone designatedherein as DNA50177 (FIG. 91; SEQ ID NO:154). The DNA50177 sequence wasthen compared to various EST databases including public EST databases(e.g., GenBank), and a proprietary EST database (LIFESEQ®, IncytePharmaceuticals, Palo Alto, Calif.) to identify homologous ESTsequences. The comparison was performed using the computer program BLASTor BLAST2 [Altschul et al., Methods in Enzymology, 266:460–480 (1996)].Those comparisons resulting in a BLAST score of 70 (or in some cases,90) or greater that did not encode known proteins were clustered andassembled into a consensus DNA sequence with the program “phrap” (PhilGreen, University of Washington, Seattle, Wash.). This consensussequence is herein designated DNA50972.

In light of an observed sequence homology between the DNA50972 consensussequence and an EST sequence encompassed within the Merck EST clone no.N33874, the Merck EST clone N33874 was purchased and the cDNA insert wasobtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.89 and is herein designated as DNA56110-1437.

The full-length DNA56110-1437 clone shown in FIG. 89 contains a singleopen reading frame with an apparent translational initiation site atnucleotide positions 77–79 and ending at the stop codon at nucleotidepositions 491–493 (FIG. 89). The predicted polypeptide precursor is 138amino acids long (FIG. 90). The full-length PRO793 protein shown in FIG.90 has an estimated molecular weight of about 15,426 daltons and a pI ofabout 10.67. Analysis of the full-length PRO793 sequence shown in FIG.90 (SEQ ID NO:153) evidences the presence of the following:transmembrane domains from about amino acid 12 to about amino acid 30,from about amino acid 33 to about amino acid 52, from about amino acid69 to about amino acid 89 and from about amino acid 93 to about aminoacid 109, potential N-myristolation sites from about amino acid 11 toabout amino acid 16, from about amino acid 51 to about amino acid 56 andfrom about amino acid 116 to about amino acid 121 and an amino acidsequence block having homology to an aminoacyl-transfer RNA synthetaseclass-II protein from about amino acid 49 to about amino acid 59. CloneDNA56110-1437 has been deposited with ATCC on Aug. 11, 1998 and isassigned ATCC deposit no. 203113.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST-2 sequence alignment analysis of the full-length sequenceshown in FIG. 90 (SEQ ID NO:153), evidenced certain homology between thePRO793 amino acid sequence and the following Dayhoff sequences: S47453,AF015193_(—)12, MTEHGNS9_(—)2, E64030, H69784, D64995, CD53_MOUSE,GEN8006, AE001138_(—)7 and COX2_STRPU.

Example 38 Isolation of cDNA Clones Encoding Human PRO1016

A consensus DNA sequence was assembled relative to other EST sequencesusing phrap as described in Example 1 above. The consensus sequenceobtained is herein designated DNA53502.

In light of an observed sequence homology between the DNA53502 consensussequence and an EST sequence encompassed within the Merck EST clone no.38680, the Merck EST clone 38680 was purchased and the cDNA insert wasobtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.92.

The entire nucleotide sequence of DNA56113-1378 is shown in FIG. 92 (SEQID NO:155). Clone DNA56113-1378 contains a single open reading framewith an apparent translational initiation site at nucleotide positions168–170 and ending at the stop codon at nucleotide positions 1302–1304(FIG. 92). The predicted polypeptide precursor is 378 amino acids long(FIG. 93). The full-length PRO1016 protein shown in FIG. 93 has anestimated molecular weight of about 44,021 daltons and a pI of about9.07. Clone DNA56113-1378 has been deposited with the ATCC. Regardingthe sequence, it is understood that the deposited clone contains thecorrect sequence, and the sequences provided herein are based on knownsequencing techniques.

Analysis of the amino acid sequence of the full-length PRO1016polypeptide suggests that portions of it possess sequence identity withacyltransferase, thereby indicating that PRO1016 may be a novelacyltransferase.

Still analyzing the amino acid sequence of SEQ ID NO:156, the putativesignal peptide is at about amino acids 1–18 of SEQ ID NO:156. Thetransmembrane domain(s) are at about amino acids 332–352 and 305–330 ofSEQ ID NO:156. The fructose-bisphosphate aldolase class-II proteinhomology sequence is at about amino acids 73–90 of SEQ ID NO:156. Theextradiol ring-cleavage dioxygenase protein is at about amino acids252–275 of SEQ ID NO:156. The corresponding nucleotides can be routinelydetermined given the sequences provided herein.

The specific Dayhoff database designation names of sequences to whichPRO1016 has sequence identity with include the following: S52645,P_R59712, P_R99249, P_R59713, BNAGPATRF_(—)1, CELT05H4_(—)15 andCELZK40_(—)1.

Example 39 Isolation of cDNA Encoding Human PRO1013

A consensus DNA sequence was assembled relative to other EST sequencesusing phrap as described in Example 1 above. The consensus DNA sequencewas then extended using repeated cycles of BLAST and phrap to extend theconsensus sequence as far as possible using the sources of ESTsequences.

In light of an observed sequence homology between the consensus sequenceand an EST sequence encompassed within the Incyte EST clone no. 3107695,the Incyte EST clone 3107695 was purchased and the cDNA insert wasobtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.94 and is herein designated as DNA56410-1414.

The entire nucleotide sequence of DNA56410-1414 is shown in FIG. 94 (SEQID NO:157). Clone DNA56410-1414 contains a single open reading framewith an apparent translational initiation site at nucleotide positions17–19 and ending at the stop codon at nucleotide positions 1244–1246(FIG. 94). The predicted polypeptide precursor is 409 amino acids long(FIG. 95). The full-length PRO1013 protein shown in FIG. 95 has anestimated molecular weight of about 46,662 daltons and a pI of about7.18. Clone DNA56410-1414 has been deposited with the ATCC. Regardingthe sequence, it is understood that the deposited clone contains thecorrect sequence, and the sequences provided herein are based on knownsequencing techniques.

Still analyzing the amino acid sequence of SEQ ID NO:158, the putativesignal peptide is at about amino acids 1–19 of SEQ ID NO:158.N-glycosylation sites are at about amino acids 75–78 and 322–325 SEQ IDNO:158. An N-myristoylation site is at about amino acids 184–189 of SEQID NO:158. A growth factor and cytokine receptor family domain is atabout amino acids 134–149 of SEQ ID NO:158. The correspondingnucleotides can be routinely determined given the sequences providedherein.

Blast analysis showed some sequence identity with other proteins.Specifically, PRO1013 has some sequence identity with at least theDayhoff sequences designated: D63877_(—)1; MHU22019_(—)1,AE000730_(—)10, and AF019079_(—)1.

Example 40 Isolation of cDNA Clones Encoding Human PRO937

A consensus DNA sequence was assembled relative to other EST sequencesusing phrap as described in Example 1 above. That consensus sequence isherein designated DNA49651. Based on the DNA49651 consensus sequence,oligonucleotides were synthesized: 1) to identify by PCR a cDNA librarythat contained the sequence of interest, and 2) for use as probes toisolate a clone of the full-length coding sequence for PRO937.

PCR primers (forward and reverse) were synthesized:

forward PCR primer 5′-CTCCGTGGTAAACCCCACAGCCC-3′ (SEQ ID NO:161); andreverse PCR primer 5′-TCACATCGATGGGATCCATGACCG-3′ (SEQ ID NO:162).Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the DNA48651 sequence which had the followingnucleotide sequence:Hybridization Probe

-   5′-GGTCTCGTGACTGTGAAGCCATGTTACAACTACTGCTCAAACATCATGAG-3′ (SEQ ID    NO:163).

In order to screen several libraries for a source of a full-lengthclone, DNA from the libraries was screened by PCR amplification with thePCR primer pair identified above. A positive library was then used toisolate clones encoding the PRO937 gene using the probe oligonucleotideand one of the PCR primers. RNA for construction of the cDNA librarieswas isolated from human fetal kidney tissue (LIB227).

DNA sequencing of the clones isolated as described above gave thefull-length DNA sequence for PRO937 [herein designated as DNA56436-1448](SEQ ID NO:159) and the derived protein sequence for PRO937.

The entire nucleotide sequence of DNA56436-1448 is shown in FIG. 96 (SEQID NO:159). It contains a single open reading frame having an apparenttranslational initiation site at nucleotide positions 499–501 and endingat the stop codon found at nucleotide positions 2167–2169 (FIG. 96, SEQID NO:159). The predicted polypeptide precursor is 556 amino acids long,has a calculated molecular weight of approximately 62,412 daltons and anestimated pI of approximately 6.62. Analysis of the full-length PRO937sequence shown in FIG. 97 (SEQ ID NO:160) evidences the presence of thefollowing features: signal peptide at about amino acids 1–22;ATP/GTP-binding site motif A (P-loop) at about amino acids 515–523; apotential N-glycosylation site at about amino acids 514–517; and sitesof glypican homology at about amino acids 54–74, 106–156, 238–279,309–345, 423–459, and 468–505.

Clone DNA56436-1448 has been deposited with ATCC on May 27, 1998, and isassigned ATCC deposit no. 209902.

Analysis of the amino acid sequence of the full-length PRO937polypeptide suggests that it possesses significant sequence similarityto glypican proteins, thereby indicating that PRO937 may be a novelglypican protein. More specifically, an analysis of the Dayhoff database(version 35.45 SwissProt 35) evidenced significant homology between thePRO937 amino acid sequence and the following Dayhoff sequences:GPCK_MOUSE, GPC2_RAT, GPC5_HUMAN, GPC3_HUMAN, P_R30168, CEC03H12_(—)2,GEN13820, HS119E23_(—)1, HDAC_DROME, and AF017637_(—)1.

Example 41 Isolation of cDNA Clones Encoding Human PRO842

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single Incyte EST cluster sequencedesignated herein as Incyte EST cluster sequence no. 69572. This ESTcluster sequence was then compared to a variety of expressed sequencetag (EST) databases which included public EST databases (e.g., GenBank)and a proprietary EST DNA database (LIFESEQ®, Incyte Pharmaceuticals,Palo Alto, Calif.) to identify existing homologies. The homology searchwas performed using the computer program BLAST or BLAST2 (Altshul etal., Methods in Enzymology 266:460–480 (1996)). Those comparisonsresulting in a BLAST score of 70 (or in some cases 90) or greater thatdid not encode known proteins were clustered and assembled into aconsensus DNA sequence with the program “phrap” (Phil Green, Universityof Washington, Seattle, Wash.). The consensus sequence obtainedtherefrom is herein designated DNA54230.

In light of an observed sequence homology between the consensus sequenceand an EST sequence encompassed within the Merck EST clone no. AA477092,the Merck EST clone AA477092 was purchased and the cDNA insert wasobtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.98 and is herein designated as DNA56855-1447.

The full length clone shown in FIG. 98 contained a single open readingframe with an apparent translational initiation site at nucleotidepositions 153–155 and ending at the stop codon found at nucleotidepositions 510–512 (FIG. 98; SEQ ID NO:164). The predicted polypeptideprecursor (FIG. 99, SEQ ID NO:165) is 119 amino acids long. PRO842 has acalculated molecular weight of approximately 13,819 Daltons and anestimated pI of approximately 11.16. Other features of PRO842 include asignal peptide at about amino acids 1–22, a potential protein kinase Cphosphorylation site at about amino acids 39–41 and two potentialN-myristoylation sites at about amino acids 27–32 and about amino acids46–51.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST-2 sequence alignment analysis of the full-length sequenceshown in FIG. 98 (SEQ ID NO:164), evidenced some homology between thePRO842 amino acid sequence and the following Dayhoff sequences:CEZK131_(—)11, P_R80843, RAT5HT2X_(—)1, S81882_(—)1, A60912,MCU60315_(—)137MC137L, U93422_(—)1, p_P91996, U93462_(—)1, andZN18_HUMAN.

Clone DNA56855-1447 was deposited with the ATCC on Jun. 23, 1998, and isassigned ATCC deposit no. 203004.

Example 42 Isolation of cDNA Clones Encoding Human PRO839

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of an EST cluster sequence from the IncyteLIFESEQ® database, designated Incyte EST Cluster No. 24479. This ESTcluster sequence was then compared to a variety of expressed sequencetag (EST) databases which included public EST databases (e.g., GenBank)and a proprietary EST DNA database (LIFESEQ®, Incyte Pharmaceuticals,Palo Alto, Calif.) to identify existing homologies. The homology searchwas performed using the computer program BLAST or BLAST2 (Altshul etal., Methods in Enzymology 266:460–480 (1996)). Those comparisonsresulting in a BLAST score of 70 (or in some cases 90) or greater thatdid not encode known proteins were clustered and assembled into aconsensus DNA sequence with the program “phrap” (Phil Green, Universityof Washington, Seattle, Wash.). The consensus sequence obtainedtherefrom is herein designated DNA55709.

In light of an observed sequence homology between the DNA55709 consensussequence and an EST sequence encompassed within the Merck EST clone no.754525, the Merck EST clone 754525 was purchased and the cDNA insert wasobtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.100 and is herein designated as DNA56859-1445.

The full length clone shown in FIG. 100 contained a single open readingframe with an apparent translational initiation site at nucleotidepositions 2–4 and ending at the stop codon found at nucleotide positions263–265 (FIG. 100; SEQ ID NO:166). The predicted polypeptide precursor(FIG. 101, SEQ ID NO:167) is 87 amino acids long. PRO839 has acalculated molecular weight of approximately 9,719 Daltons and anestimated pI of approximately 4.67. Other features of PRO839 include asignal peptide at about amino acids 1–23, potential protein kinase Cphosphorylation sites at about amino acids 37–39 and about amino acids85–87, a potential casein kinase II phosphorylation site at about aminoacids 37–40, sequence identity with ribonucleotide reductase largesubunit protein at about amino acids 50–60, and sequence identity witheukaryotic RNA-binding region RNP-1 proteins at about amino acids 70–79.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST-2 sequence alignment analysis of the full-length sequenceshown in FIG. 101 (SEQ ID NO:167), evidenced some homology between thePRO839 amino acid sequence and the following Dayhoff sequences:CD14_MOUSE, XPR6_YARLI, HS714385_(—)1, S49783, BB19_RABIT, GVPH-HALME,AB003135_(—)1, P_R85453, LUU27081_(—)2, and TP2B_MOUSE.

Clone DNA56859-1445 was deposited with the ATCC on Jun. 23, 1998, and isassigned ATCC deposit no. 209019.

Example 43 Isolation of cDNA Clones Encoding Human PRO1180

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single Incyte EST cluster sequence (IncyteEST cluster sequence no. 14732). The Incyte EST cluster sequence no.14732 sequence was then compared to a variety of expressed sequence tag(EST) databases which included public EST databases (e.g., GenBank) anda proprietary EST DNA database (LIFESEQ™, Incyte Pharmaceuticals, PaloAlto, Calif.) to identify existing homologies. The homology search wasperformed using the computer program BLAST or BLAST2 (Altshul et al.,Methods in Enzymology 266:460–480 (1996)). Those comparisons resultingin a BLAST score of 70 (or in some cases 90) or greater that did notencode known proteins were clustered and assembled into a consensus DNAsequence with the program “phrap” (Phil Green, University of Washington,Seattle, Wash.). The consensus sequence obtained therefrom is hereindesignated DNA55711.

In light of an observed sequence homology between the DNA55711 consensussequence and an EST sequence encompassed within the Merck EST clone no.T60981, the Merck EST clone T60981 was purchased and the cDNA insert wasobtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.102 and is herein designated DNA56860-1510.

The full length clone shown in FIG. 102 contained a single open readingframe with an apparent translational initiation site at nucleotidepositions 78–80 and ending at the stop codon found at nucleotidepositions 909–911 (FIG. 102; SEQ ID NO:168). The predicted polypeptideprecursor is 277 amino acids long, has a calculated molecular weight ofapproximately 31,416 daltons and an estimated pI of approximately 8.88.Analysis of the full-length PRO1180 sequence shown in FIG. 103 (SEQ IDNO:169) evidences the presence of the following: a signal peptide fromabout amino acid 1 to about amino acid 23, a leucine zipper patternsequence from about amino acid 10 to about amino acid 31, and potentialN-myristolation sited from about amino acid 64 to about amino acid 69,from about amino acid 78 to about amino acid 83, from about amino acid80 to about amino acid 85, from about amino acid 91 to about amino acid96 and from about amino acid 201 to about amino acid 206. CloneDNA56860-1510 has been deposited with the ATCC on Jun. 9, 1998 and isassigned ATCC deposit no. 209952.

Analysis of the amino acid sequence of the full-length PRO1180polypeptide suggests that it possesses sequence similarity to themethyltransferase family of proteins. More specifically, an analysis ofthe Dayhoff database (version 35.45 SwissProt 35) evidenced some degreeof homology between the PRO1180 amino acid sequence and the followingDayhoff sequences, MTCI65_(—)14, D69267, YH09_YEAST, BIOC_SERMA,ATAC00448415T1D16.16, SHGCPIR_(—)18, SPBC3B9_(—)4, AB009504_(—)14,P_W17977 and A69952.

Example 44 Isolation of cDNA Clones Encoding Human PRO1134

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of an EST cluster sequence from the Incytedatabase, designated 7511. This EST cluster sequence was then comparedto a variety of expressed sequence tag (EST) databases which includedpublic EST databases (e.g., GenBank) and a proprietary EST DNA database(Lifeseq®, Incyte Pharmaceuticals, Palo Alto, Calif.) to identifyexisting homologies. The homology search was performed using thecomputer program BLAST or BLAST2 (Altshul et al., Methods in Enzymology266:460–480 (1996)). Those comparisons resulting in a BLAST score of 70(or in some cases 90) or greater that did not encode known proteins wereclustered and assembled into a consensus DNA sequence with the program“phrap” (Phil Green, University of Washington, Seattle, Wash.). Theconsensus sequence obtained therefrom is herein designated DNA55725. Twoproprietary Genentech EST sequences were employed in the assembly andare shown in FIG. 106 (SEQ ID NO:172) and FIG. 107 (SEQ ID NO:173).

In light of an observed sequence homology between the DNA55725 consensussequence and an EST sequence encompassed within the Merck EST clone no.H94897, the Merck EST clone H94897 was purchased and the cDNA insert wasobtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.106 and is herein designated as DNA56865-1491.

Clone DNA56865-1491 contains a single open reading frame with anapparent translational initiation site at nucleotide positions 153–155and ending at the stop codon at nucleotide positions 1266–1268 (FIG.104). The predicted polypeptide precursor is 371 amino acids long (FIG.105). The full-length PRO1134 protein shown in FIG. 105 has an estimatedmolecular weight of about 41,935 daltons and a pI of about 9.58.Analysis of the full-length PRO1134 sequence shown in FIG. 105 (SEQ IDNO:171) evidences the presence of the following: a signal peptide fromabout amino acid 1 to about amino acid 23, potential N-glycosylationsites from about amino acid 103 to about amino acid 106, from aboutamino acid 249 to about amino acid 252 and from about amino acid 257 toabout amino acid 260, and an amino acid block having homology totyrosinase CuA-binding region proteins from about amino acid 280 toabout amino acid 306. Clone DNA56865-1491 has been deposited with ATCCon Jun. 23, 1998 and is assigned ATCC deposit no. 203022.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST-2 sequence alignment analysis of the full-length sequenceshown in FIG. 105 (SEQ ID NO:171), evidenced significant homologybetween the PRO1134 amino acid sequence and the following Dayhoffsequences: F20P5_(—)18, AC002396_(—)10, S47847, C64146, GSPA_BACSU,P_W10564, RFAI_ECOLI, Y258_HAEIN, RFAJ_SALTY and P_R32985.

Example 45 Isolation of cDNA Clones Encoding Human PRO830

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of an EST cluster sequence from theIncytedatabase, designated 20251. This EST cluster sequence was thencompared to a variety of expressed sequence tag (EST) databases whichincluded public EST databases (e.g., GenBank) and a proprietary EST DNAdatabase (LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, Calif.) toidentify existing homologies. The homology search was performed usingthe computer program BLAST or BLAST2 (Altshul et al., Methods inEnzymology 266:460–480 (1996)). Those comparisons resulting in a BLASTscore of 70 (or in some cases 90) or greater that did not encode knownproteins were clustered and assembled into a consensus DNA sequence withthe program “phrap” (Phil Green, University of Washington, Seattle,Wash.). The consensus sequence obtained therefrom is herein designatedDNA55733.

In light of an observed sequence homology between the DNA55733 consensussequence and an EST sequence encompassed within the Merck EST clone no.H78534, the Merck EST clone H78534 was purchased and the cDNA insert wasobtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.108 and is herein designated as DNA56866-1342.

Clone DNA56866-1342 contains a single open reading frame with anapparent translational initiation site at nucleotide positions 154–156and ending at the stop codon at nucleotide positions 415–417 (FIG. 108).The predicted polypeptide precursor is 87 amino acids long (FIG. 109).The full-length PRO830 protein shown in FIG. 109 has an estimatedmolecular weight of about 9,272 daltons and a pI of about 9.19. Analysisof the fall-length PRO830 sequence shown in FIG. 109 (SEQ ID NO:175)evidences the presence of the following: a signal peptide from aboutamino acid 1 to about amino acid 33, potential N-myristoylation sitesfrom about amino acid 2 to about amino acid 7 and from about amino acid8 to about amino acid 13 and a thioredoxin family of proteins homologyblock from about amino acid 23 to about amino acid 39. Clone UNQ470(DNA56866-1342) has been deposited with ATCC on Jun. 22, 1998 and isassigned ATCC deposit no. 203023.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST-2 sequence alignment analysis of the full-length sequenceshown in FIG. 109 (SEQ ID NO:175), evidenced significant homologybetween the PRO830 amino acid sequence and the following Dayhoffsequences: HSU88154_(—)1, HSU88153_(—)1, SAPKSGENE_(—)1, HPU31791_(—)5,GGCNOT2_(—)1, CPU91421_(—)1, CHKESTPC09_(—)1, PQ0769, U97553_(—)79 andB60095.

Example 46 Isolation of cDNA Clones Encoding Human PRO1115

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of an EST cluster sequence from the LIFESEQ®database, designated Incyte EST cluster sequence no. 165008. This ESTcluster sequence was then compared to a variety of expressed sequencetag (EST) databases which included public EST databases (e.g., GenBank)and a proprietary EST DNA database (LIFESEQ®, Incyte Pharmaceuticals,Palo Alto, Calif.) to identify existing homologies. The homology searchwas performed using the computer program BLAST or BLAST2 (Altshul etal., Methods in Enzymology 266:460–480 (1996)). Those comparisonsresulting in a BLAST score of 70 (or in some cases 90) or greater thatdid not encode known proteins were clustered and assembled into aconsensus DNA sequence with the program “phrap” (Phil Green, Universityof Washington, Seattle, Wash.). The consensus sequence obtainedtherefrom is herein designated DNA55726.

In light of an observed sequence homology between the DNA55726 consensussequence and an EST sequence encompassed within the Merck EST clone no.R75784, the Merck EST clone R75784 was purchased and the cDNA insert wasobtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.111 and is herein designated as DNA56868-1478.

The full length clone shown in FIG. 110 contained a single open readingframe with an apparent translational initiation site at nucleotidepositions 189–191 and ending at the stop codon found at nucleotidepositions 1524–1526 (FIG. 110; SEQ ID NO:176). The predicted polypeptideprecursor (FIG. 111, SEQ ID NO:177) is 445 amino acids long. PRO1115 hasa calculated molecular weight of approximately 50,533 Daltons and anestimated pI of approximately 8.26. Additional features include a signalpeptide at about amino acids 1–20; potential N-glycosylation sites atabout amino acids 204–207, 295–298, and 313–316; and putativetransmembrane domains at about amino acids 35–54, 75–97, 126–146,185–204, 333–350, and 353–371.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST-2 sequence alignment analysis of the full-length sequenceshown in FIG. 111 (SEQ ID NO:177), evidenced some amino acid sequenceidentity between the PRO1115 amino acid sequence and the followingDayhoff sequences: AF053947_(—)79, S73698, CEC47A10_(—)4,CCOMTNDS5G_(—)1, HS4LMP2AC_(—)1, LMP2_EBV, PA24_MOUSE, HCU33331_(—)7,P-W05508, and AF002273_(—)1.

Clone DNA56868-1478 was deposited with the ATCC on Jun. 23, 1998 and isassigned ATCC deposit no. 203024.

Example 47 Isolation of cDNA Clones Encoding Human PRO1277

A consensus DNA sequence was assembled relative to other ESTs usingrepeated cycles of BLAST and the program “phrap” as described in Example1 above. One or more of the ESTs from the assembly was derived fromdiseased coronary artery tissue. The consensus sequence obtained isdesignated herein as “DNA49434”.

In light of an observed sequence homology between the DNA49434 consensussequence and an EST sequence encompassed within the Incyte EST clone no.3042605, the Incyte EST clone 3042605 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.112 (SEQ ID NO:178).

Clone DNA56869-1545 contains a single open reading frame with anapparent translational initiation site at nucleotide positions 188–190,and an apparent stop codon at nucleotide positions 2222–2224 (FIG. 112).The predicted polypeptide precursor is 678 amino acids long (FIG. 113).The full-length PRO1277 protein shown in FIG. 113 has an estimatedmolecular weight of about 73,930 daltons and a pI of about 9.48.Additional features include a signal peptide at about amino acids 1–26;a transmembrane domain at about amino acids 181–200, and potentialN-glycosylation sites at about amino acids 390–393 and 520–523.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST-2 sequence alignment analysis of the full-length sequenceshown in FIG. 113 (SEQ ID NO:179), revealed significant homology betweenthe PRO1277 amino acid sequence and Dayhoff sequence no AF012252_(—)1.Homology was also found between the PRO1277 amino acid sequence and thefollowing Dayhoff sequences: AF006740_(—)1, CA36_HUMAN, HSU1_(—)1,HUMCOL7A1X_(—)1, CA17_HUMAN, MMZ78163_(—)1, CAMA_CHICK, HSU69263_(—)1,YNX3_CAEEL, and MMRNAM3_(—)1.

Clone DNA56869-1545 has been deposited with ATCC and is assigned ATCCdeposit no. 203161.

Example 48 Isolation of cDNA Clones Encoding Human PRO1135

A consensus DNA sequence was assembled relative to other EST sequencesusing phrap as described in Example 1 above. This consensus sequence isherein designated DNA52767. Based on the DNA52767 consensus sequence,oligonucleotides were synthesized: 1) to identify by PCR a cDNA librarythat contained the sequence of interest, and 2) for use as probes toisolate a clone of the full-length coding sequence for PRO1135.

In order to screen several libraries for a source of a full-lengthclone, DNA from the libraries was screened by PCR amplification with PCRprimer pairs prepared based upon the DNA52767 sequence. A positivelibrary was then used to isolate clones encoding the PRO1135 gene usingthe probe oligonucleotide and one of the PCR primers. RNA forconstruction of the cDNA libraries was isolated from human coronaryartery smooth muscle tissue (LIB309). The cDNA libraries used to isolatethe cDNA clones were constructed by standard methods using commerciallyavailable reagents such as those from Invitrogen, San Diego, Calif. ThecDNA was primed with oligo dT containing a NotI site, linked with bluntto SalI hemikinased adaptors, cleaved with NotI, sized appropriately bygel electrophoresis, and cloned in a defined orientation into a suitablecloning vector (such as pRKB or pRKD; pRK5B is a precursor of pRK5D thatdoes not contain the SfiI site; see, Holmes et al., Science,253:1278–1280 (1991)) in the unique XhoI and NotI sites.

DNA sequencing of the clones isolated as described above gave thefull-length DNA sequence for PRO1135 [herein designated asDNA56870-1492] (SEQ ID NO:180) and the derived protein sequence forPRO1135.

The entire nucleotide sequence of DNA56870-1492 is shown in FIG. 114(SEQ ID NO:180). Clone DNA56870-1492 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 62–64 and ending at the stop codon at nucleotide positions1685–1687 (FIG. 114). The predicted polypeptide precursor is 541 aminoacids long (FIG. 115). The full-length PRO1135 protein shown in FIG. 115has an estimated molecular weight of about 60,335 daltons and a pI ofabout 5.26. Analysis of the full-length PRO1135 sequence shown in FIG.115 (SEQ ID NO:181) evidences the presence of the following: a signalpeptide from about amino acid 1 to about amino acid 21, potentialN-glycosylation sited from about amino acid 53 to about amino acid 56,from about amino acid 75 to about amino acid 78, from about amino acid252 to about amino acid 255 and from about amino acid 413 to about aminoacid 416 and an amino acid block having homology to glycosyl hydrolasefamily 35 proteins from about amino acid 399 to about amino acid 414.Clone DNA56870-1492 has been deposited with ATCC on Jun. 2, 1998 and isassigned ATCC deposit no. 209925.

Analysis of the amino acid sequence of the full-length PRO1135polypeptide suggests that it possesses significant sequence similarityto the alpha 1,2-mannosidase protein, thereby indicating that PRO1135may be a novel mannosidase. More specifically, an analysis of theDayhoff database (version 35.45 SwissProt 35) evidenced significanthomology between the PRO1135 amino acid sequence and the followingDayhoff sequences, DMC86E4_(—)5, D86967_(—)1, SPAC23A1_(—)4, YH04_YEAST,B54408, SSMAN9MAN_(—)1, CEZC410_(—)4, S61631 and MSU14190_(—)1.

Example 49 Isolation of cDNA Clones Encoding Human PRO1114

A cDNA sequence isolated in the amylase screen described in Example 2above was found, by the WU-BLAST-2 sequence alignment computer program,to have certain sequence identity to other known interferon receptors.This cDNA sequence is herein designated DNA48466 and is shown in FIG.118 (SEQ ID NO:184). Based on the sequence identity, probes weregenerated from the sequence of the DNA48466 molecule and used to screena human breast carconoma library (LIB135) prepared as described inparagraph 1 of Example 2 above. The cloning vector was pRK5B (pRK5B is aprecursor of pRK5D that does not contain the SfiI site; see, Holmes etal., Science, 253:1278–1280 (1991)), and the cDNA size cut was less than2800 bp.

The oligonucleotide probes employed were as follows:

forward PCR primer 5′-AGGCTTCGCTGCGACTAGACCTC-3′ (SEQ ID NO:185) reversePCR primer 5′-CCAGGTCGGGTAAGGATGGTTGAG-3′ (SEQ ID NO:186) hybridizationprobe 5′-TTTCTACGCATTGATTCCATGTTTGCTCA (SEQ ID NO:187)CAGATGAAGTGGCCATTCTGC-3′

A full length clone was identified that contained a single open readingframe with an apparent translational initiation site at nucleotidepositions 250–252, and a stop signal at nucleotide positions 1183–1185(FIG. 116, SEQ ID NO:182). The predicted polypeptide precursor is 311amino acids long, has a calculated molecular weight of approximately35,076 daltons and an estimated pI of approximately 5.04. Analysis ofthe full-length PRO1114 interferon receptor sequence shown in FIG. 117(SEQ ID NO:183) evidences the presence of the following: a signalpeptide from about amino acid 1 to about amino acid 29, a transmembranedomain from about amino acid 230 to about amino acid 255, potentialN-glycosylation sites from about amino acid 40 to about amino acid 43and from about amino acid 134 to about amino acid 137, an amino acidsequence block having homology to tissue factor proteins from aboutamino acid 92 to about amino acid 119 and an amino acid sequence blockhaving homology to integrin alpha chain proteins from about amino acid232 to about amino acid 262. Clone DNA57033-1403 has been deposited withATCC on May 27, 1998 and is assigned ATCC deposit no. 209905.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST-2 sequence alignment analysis of the full-length sequenceshown in FIG. 117 (SEQ ID NO:183), evidenced significant homologybetween the PRO1114 interferon receptor amino acid sequence and thefollowing Dayhoff sequences: G01418, INR1_MOUSE, P_R71035, INGS_HUMAN,A26595_(—)1, A26593_(—)1, I56215 and TF_HUMAN.

Example 50 Isolation of cDNA Clones Encoding Human PRO828

A consensus DNA sequence was identified using the method described inExample 1 above. This consensus sequence is herein designated DNA35717.Based on the DNA35717 consensus sequence, oligonucleotides weresynthesized: 1) to identify by PCR a cDNA library that contained thesequence of interest, and 2) for use as probes to isolate a clone of thefull-length coding sequence for PRO828.

PCR primers (forward and reverse) were synthesized:

forward PCR primer 5′-GCAGGACTTCTACGACTTCAAGGC-3′ (SEQ ID NO:190); andreverse PCR primer 5′-AGTCTGGGCCAGGTACTTGAAGGC-3 (SEQ ID NO:191).Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the consensus DNA35717 sequence which had the followingnucleotide sequence:Hybridization Probe

-   5′-CAACATCCGGGGCAAACTGGTGTCGCTGGAGAAGTACCGCGGATCGGTGT-3′ (SEQ ID    NO:192)

In order to screen several libraries for a source of a full-lengthclone, DNA from the libraries was screened by PCR amplification with thePCR primer pair identified above. A positive library was then used toisolate clones encoding the PRO828 gene using the probe oligonucleotideand one of the PCR primers. RNA for construction of the cDNA librarieswas isolated from human fetal lung tissue (LIB25).

DNA sequencing of the clones isolated as described above gave thefull-length DNA sequence for PRO828 [herein designated as DNA57037-1444](SEQ ID NO:188) and the derived protein sequence for PRO828.

The entire nucleotide sequence of DNA57037-1444 is shown in FIG. 119(SEQ ID NO:188). Clone DNA57037-1444 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 34–36 and ending at the stop codon at nucleotide positions595–597 (FIG. 119). The predicted polypeptide precursor is 187 aminoacids long (FIG. 120). The full-length PRO828 protein shown in FIG. 120has an estimated molecular weight of about 20,996 daltons and a pI ofabout 8.62. Analysis of the full-length PRO828 sequence shown in FIG.120 (SEQ ID NO:189) evidences the presence of the following: a signalpeptide at about amino acids 1–21; sequences identity to glutathioneperoxidases signature 2 at about amino acids 82–89; sequence identity toglutathione peroxidases selenocysteine proteins at about amino acids35–60, 63–100, 107–134, and 138–159. Clone DNA57037-1444 has beendeposited with ATCC on May 27, 1998, and is assigned ATCC deposit no.209903.

Analysis of the amino acid sequence of the full-length PRO828polypeptide suggests that it possesses significant sequence similarityto glutathione peroxidases, thereby indicating that PRO828 may be anovel peroxidase enzyme. More specifically, an analysis of the Dayhoffdatabase (version 35.45 SwissProt 35) evidenced sequence identitybetween the PRO828 amino acid sequence and the following Dayhoffsequences: AF053311_(—)1, CELT09A12_(—)2, AC004151_(—)3, BTUE_ECOLI,CER05H10_(—)3, P_P80918, PWU88907_(—)1, and P_W22308.

Example 51 Isolation of cDNA Clones Encoding Human PRO1009

A cDNA clone (DNA57129-1413) encoding a native human PRO1009 polypeptidewas identified by the use of a yeast screen, in a human SK-Lu-1adenocarcinoma cell line cDNA library that preferentially represents the5′ ends of the primary cDNA clones. First SEQ ID NO:195 (FIG. 123) wasidentified, which was extended by alignments to other EST sequences toform a consensus sequence. Oligonucleotide probes based upon theconsensus sequence were synthesized and used to screen the cDNA librarywhich gave rise to the full-length DNA57129-1413 clone.

The full length DNA57129-1413 clone shown in FIG. 121 contained a singleopen reading frame with an apparent translational initiation site atnucleotide positions 41–43 and ending at the stop codon found atnucleotide positions 1886–1888 (FIG. 121; SEQ ID NO:193). The predictedpolypeptide precursor (FIG. 122, SEQ ID NO:194) is 615 amino acids long.FIG. 122 also shows the approximate locations of the signal sequence,transmembrane domains, myristoylation sites, a glycosylation site and anAMP-binding domain. PRO1009 has a calculated molecular weight ofapproximately 68,125 daltons and an estimated pI of approximately 7.82.Clone DNA57129-1413 has been deposited with ATCC and is assigned ATCCdeposit no. 209977. It is understood that the deposited clone has theactual and correct sequence and that the representations herein may haveminor, normal sequencing errors.

Based on a WU-BLAST-2 sequence alignment analysis (using the ALIGNcomputer program) of the full-length sequence, PRO1009 shows amino acidsequence identity to at least the following proteins which weredesignated in a Dayhoff database as follows: F69893, CEF28F8_(—)2,BSY13917_(—)7, BSY13917_(—)7, D69187, D69649, XCRPFB_(—)1, E64928,YDID_ECOLI, BNACSF8_(—)1 and RPU75363_(—)2.

Example 52 Isolation of cDNA Clones Encoding Human PRO1007

A consensus DNA sequence was assembled relative to other EST sequencesusing phrap as described in Example 1 above. This consensus sequence isherein designated as DNA40671.

In light of an observed sequence homology between the DNA40671 consensussequence and an EST sequence encompassed within the Merck EST clone no.T70513, the Merck EST clone T70513 was purchased and the cDNA insert wasobtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.124.

The entire nucleotide sequence of DNA57690-1374 is shown in FIG. 124(SEQ ID NO:196). Clone DNA57690-1374 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 16–18 and ending at the stop codon at nucleotide positions1054–1056 (FIG. 124). The predicted polypeptide precursor is 346 aminoacids long (FIG. 125). The full-length PRO1007 protein shown in FIG. 125has an estimated molecular weight of about 35,971 daltons and a pI ofabout 8.17. Clone DNA57690-1374 has been deposited with the ATCC on Jun.9, 1998. Regarding the sequence, it is understood that the depositedclone contains the actual sequence, and the sequences provided hereinare based on known sequencing techniques. The representative figuresherein show the representative numbering.

Analysis of the amino acid sequence of the full-length PRO1007polypeptide suggests that portions of it possess sequence identity toMAGPIAP, thereby indicating that PRO1007 may be a novel member of thefamily to which MAGPIAP belongs.

Still analyzing the amino acid sequence of SEQ ID NO:197, the putativesignal peptide is at about amino acids 1–30 of SEQ ID NO:197. Thetransmembrane domain is at amino acids 325–346 of SEQ ID NO:197.N-glycosylation sites are at about amino acids 118–121, 129–132,163–166, 176–179, 183–186 and 227–130 of SEQ ID NO:197. Ly-6/u-Pardomain protein homology is at about amino acids 17–36 and 209–222 of SEQID NO:197. The coresponding nucleotides of the amino acids presentedherein can be routinely determined given the sequences provided herein.

Example 53 Isolation of cDNA Clones Encoding Human PRO1056

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of an EST cluster sequence from the Incytedatabase, designated herein as 6425. This EST cluster sequence was thencompared to a variety of expressed sequence tag (EST) databases whichincluded public EST databases (e.g., GenBank) and a proprietary EST DNAdatabase (Lifeseq®, Incyte Pharmaceuticals, Palo Alto, Calif.) toidentify existing homologies. The homology search was performed usingthe computer program BLAST or BLAST2 (Altshul et al., Methods inEnzmology 266:460–480 (1996)). Those comparisons resulting in a BLASTscore of 70 (or in some cases 90) or greater that did not encode knownproteins were clustered and assembled into a consensus DNA sequence withthe program “phrap” (Phil Green, University of Washington, Seattle,Wash.). The consensus sequence obtained therefrom is herein designatedDNA55736.

In light of an observed sequence homology between the DNA55736 consensussequence and an EST sequence encompassed within the Merck EST clone no.R88049, the Merck EST clone R88049 was purchased and the cDNA insert wasobtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.126 and is herein designated as DNA57693-1424.

Clone DNA57693-1424 contains a single open reading frame with anapparent translational initiation site at nucleotide positions 56–58 andending at the stop codon at nucleotide positions 416–418 (FIG. 126). Thepredicted polypeptide precursor is 120 amino acids long (FIG. 127). Thefull-length PRO1056 protein shown in FIG. 127 has an estimated molecularweight of about 13,345 daltons and a pI of about 5.18. Analysis of thefull-length PRO1056 sequence shown in FIG. 127 (SEQ ID NO:199) evidencesthe presence of the following: a signal peptide from about amino acid 1to about amino acid 18, a transmembrane domain from about amino acid 39to about amino acid 58, a potential N-glycosylation site from aboutamino acid 86 to about amino acid 89, protein kinase C phosphorylationsites from about amino acid 36 to about amino acid 38 and from aboutamino acid 58 to about amino acid 60, a tyrosine kinase phosphorylationsite from about amino acid 25 to about amino acid 32 and an amino acidsequence block having homology to channel forming colicin proteins fromabout amino acid 24 to about amino acid 56. Clone DNA57693-1424 has beendeposited with ATCC on Jun. 23, 1998 and is assigned ATCC deposit no.203008.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST-2 sequence alignment analysis of the full-length sequenceshown in FIG. 127 (SEQ ID NO:199), evidenced significant homologybetween the PRO1056 amino acid sequence and the following Dayhoffsequences: PLM_HUMAN, A40533, ATNG_HUMAN, A55571, ATNG_SHEEP, S31524,GEN13025, RIC_MOUSE, A48678 and A10871_(—)1.

Example 54 Isolation of cDNA Clones Encoding Human PRO826

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of an EST cluster sequence from the Incytedatabase, designated 47283. This EST cluster sequence was then comparedto a variety of expressed sequence tag (EST) databases which includedpublic EST databases (e.g., GenBank) and a proprietary EST DNA database(LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, Calif.) to identifyexisting homologies. The homology search was performed using thecomputer program BLAST or BLAST2 (Altshul et al., Methods in Enzymology266:460–480 (1996)). Those comparisons resulting in a BLAST score of 70(or in some cases 90) or greater that did not encode known proteins wereclustered and assembled into a consensus DNA sequence with the program“phrap” (Phil Green, University of Washington, Seattle, Wash.). Theconsensus sequence obtained therefrom is herein designated DNA56000.

In light of an observed sequence homology between the DNA56000 consensussequence and an EST sequence encompassed within the Merck EST clone no.W69233, the Merck EST clone W69233 was purchased and the cDNA insert wasobtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.128 and is herein designated as DNA57694–1341.

Clone DNA57694-1341 contains a single open reading frame with anapparent translational initiation site at nucleotide positions 13–15 andending at the stop codon at nucleotide positions 310–312 (FIG. 128). Thepredicted polypeptide precursor is 99 amino acids long (FIG. 129). Thefull-length PRO826 protein shown in FIG. 129 has an estimated molecularweight of about 11,050 daltons and a pI of about 7.47. Analysis of thefull-length PRO826 sequence shown in FIG. 129 (SEQ ID NO:201) evidencesthe presence of the following: a signal peptide from about amino acid 1to about amino acid 22, potential N-myristoylation sites from aboutamino acid 22 to about amino acid 27 and from about amino acid 90 toabout amino acid 95 and an amino acid sequence block having homology toperoxidase from about amino acid 16 to about amino acid 48. CloneDNA57694-1341 has been deposited with ATCC on Jun. 22, 1998 and isassigned ATCC deposit no. 203017.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST-2 sequence alignment analysis of the full-length sequenceshown in FIG. 129 (SEQ ID NO:201), evidenced significant homologybetween the PRO826 amino acid sequence and the following Dayhoffsequences: CCU12315_(—)1, SCU96108_(—)6, CELF39F10_(—)4 and HELT_HELHO.

Example 55 Isolation of cDNA Clones Encoding Human PRO819

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of an EST cluster sequence from the Incytedatabase, designated 49605. This EST cluster sequence was then comparedto a variety of expressed sequence tag (EST) databases which includedpublic EST databases (e.g., GenBank) and a proprietary EST DNA database(LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, Calif.) to identifyexisting homologies. The homology search was performed using thecomputer program BLAST or BLAST2 (Altshul et al., Methods in Enzymology266:460–480 (1996)). Those comparisons resulting in a BLAST score of 70(or in some cases 90) or greater that did not encode known proteins wereclustered and assembled into a consensus DNA sequence with the program“phrap” (Phil Green, University of Washington, Seattle, Wash.). Theconsensus sequence obtained therefrom is herein designated DNA56015.

In light of an observed sequence homology between the DNA56015 consensussequence and an EST sequence encompassed within the Merck EST clone no.H65785, the Merck EST clone H65785 was purchased and the cDNA insert wasobtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.130 and is herein designated as DNA57695-1340.

Clone DNA57695-1340 contains a single open reading frame with anapparent translational initiation site at nucleotide positions 46–48 andending at the stop codon at nucleotide positions 202–204 (FIG. 130). Thepredicted polypeptide precursor is 52 amino acids long (FIG. 131). Thefull-length PRO819 protein shown in FIG. 131 has an estimated molecularweight of about 5,216 daltons and a pI of about 4.67. Analysis of thefull-length PRO819 sequence shown in FIG. 131 (SEQ ID NO:203) evidencesthe presence of the following: a signal peptide from about amino acid 1to about amino acid 24, a potential N-myristoylation site from aboutamino acid 2 to about amino acid 7 and a region having homology toimmunoglobulin light chain from about amino acid 5 to about amino acid33. Clone DNA57695-1340 has been deposited with ATCC on Jun. 23, 1998and is assigned ATCC deposit no. 203006.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 131 (SEQ ID NO:203), evidenced significant homologybetween the PRO819 amino acid sequence and the following Dayhoffsequences: HSU03899_(—)1, HUMIGLITEB_(—)1, VG28_HSVSA, AF031522_(—)1,PAD1_YEAST and AF045484_(—)1.

Example 56 Isolation of cDNA Clones Encoding Human PRO1006

An initial candidate sequence from Incyte cluster sequence no. 45748 wasidentified using the signal algorithm process described in Example 3above. This sequence was then aligned with a variety of public andIncyte EST sequences and a consensus sequence designated herein asDNA56036 was derived therefrom.

In light of an observed sequence homology between the DNA56036 consensussequence and an EST sequence encompassed within the Merck EST clone no.489737, the Merck EST clone 489737 was purchased and the cDNA insert wasobtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.132.

The entire nucleotide sequence of DNA57699-1412 is shown in FIG. 132(SEQ ID NO:204). Clone DNA57699-1412 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 28–30 and ending at the stop codon at nucleotide positions1204–1206 (FIG. 132). The predicted polypeptide precursor is 392 aminoacids long (FIG. 133). The full-length PRO1006 protein shown in FIG. 133has an estimated molecular weight of about 46,189 daltons and a pI ofabout 9.04. Clone DNA57699-1412 has been deposited with the ATCC.Regarding the sequence, it is understood that the deposited clonecontains the correct sequence, and the sequences provided herein arebased on known sequencing techniques.

Analyzing the amino acid sequence of SEQ ID NO:205, the putative signalpeptide is at about amino acids 1–23 of SEQ ID NO:205. TheN-glycosylation sites are at about amino acids 40–43, 53–56, 204–207,and 373–376 of SEQ ID NO:205. An N-myristoylation site is at about aminoacids 273–278 of SEQ ID NO:205. The corresponding nucleotides of theseamino acid regions and others can be routinely determined given thesequences provided herein.

Example 57 Isolation of cDNA Clones Encoding Human PRO1112

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a specific EST cluster sequence. This ESTcluster sequence was then compared to a variety of expressed sequencetag (EST) databases which included public EST databases (e.g., GenBank)and a proprietary EST DNA database (LIFESEQ®, Incyte Pharmaceuticals,Palo Alto, Calif.) to identify existing homologies. The homology searchwas performed using the computer program BLAST or BLAST2 (Altshul etal., Methods in Enzymology 266:460–480 (1996)). Those comparisonsresulting in a BLAST score of 70 (or in some cases 90) or greater thatdid not encode known proteins were clustered and assembled into aconsensus DNA sequence with the program “phrap” (Phil Green, Universityof Washington, Seattle, Wash.). The consensus sequence obtainedtherefrom is herein designated DNA56018.

In light of an observed sequence homology between the DNA56018 consensussequence and an EST sequence encompassed within the Merck EST clone no.AA223546, the Merck EST clone AA223546 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.134 and is herein designated as DNA57702-1476.

The entire nucleotide sequence of DNA57702-1476 is shown in FIG. 134(SEQ ID NO:206). Clone DNA57702-1476 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 20–22 and ending at the stop codon at nucleotide positions806–808 of SEQ ID NO:206 (FIG. 134). The predicted polypeptide precursoris 262 amino acids long (FIG. 135). The full-length PRO1112 proteinshown in FIG. 135 has an estimated molecular weight of about 29,379daltons and a pI of about 8.93. FIG. 135 also shows the approximatelocations of the signal peptide and transmembrane domains. CloneDNA57702-1476 has been deposited with the ATCC on Jun. 9, 1998. It isunderstood that the deposited clone has the actual nucleic acid sequenceand that the sequences provided herein are based on known sequencingtechniques.

Analysis of the amino acid sequence of the full-length PRO1112polypeptide suggests that it possesses some sequence similarity to otherproteins. More specifically, an analysis of the Dayhoff database(version 35.45 SwissProt 35) evidenced some sequence identity betweenthe PRO1112 amino acid sequence and at least the following Dayhoffsequences, MTY20B11_(—)13 (a mycobacterium tuberculosis peptide),F64471, AE000690_(—)6, XLU16364_(—)1, E43259 (H+-transporting ATPsynthase) and PIGSLADRXE_(—)1 (MHC class II histocompatibility antigen).

Example 58 Isolation of cDNA Clones Encoding Human PRO1074

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single Incyte EST cluster sequence (Incytecluster sequence No. 42586). This cluster sequence was then compared toa variety of expressed sequence tag (EST) databases which includedpublic EST databases (e.g., GenBank) and a proprietary EST DNA database(LIFESEQ™, Incyte Pharmaceuticals, Palo Alto, Calif.) to identifyexisting homologies. The homology search was performed using thecomputer program BLAST or BLAST2 (Altshul et al., Methods in Enzymology266:460–480 (1996)). Those comparisons resulting in a BLAST score of 70(or in some cases 90) or greater that did not encode known proteins wereclustered and assembled into a consensus DNA sequence with the program“phrap” (Phil Green, Univ. of Washington, Seattle, Wash.). The consensussequence obtained therefrom is herein designated DNA56251.

In light of an observed sequence homology between the DNA56251 consensussequence and an EST sequence encompassed within the Merck EST clone no.AA081912, the Merck EST clone AA081912 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.136 and is the full-length DNA sequence for PRO1074. Clone DNA57704-1452was deposited with the ATCC on Jun. 9, 1998, and is assigned ATCCdeposit no. 209953.

The entire nucleotide sequence of DNA57704-1452 is shown in FIG. 136(SEQ ID NO:208). Clone DNA57704-1452 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 322–324 and ending at the stop codon at nucleotide positions1315–1317 (FIG. 136). The predicted polypeptide precursor is 331 aminoacids long (FIG. 137). The full-length PRO1074 protein shown in FIG. 137has an estimated molecular weight of about 39,512 Daltons and a pI ofabout 8.03. Analysis of the full-length PRO1074 sequence shown in FIG.137 (SEQ ID NO:209) evidences the presence of the following features: atransmembrane domain at about amino acids 20 to 39; potentialN-glycosylation sites at about amino acids 72 to 75, 154 to 157, 198 to201, 212 to 215, and 326 to 329; a glycosaminoglycan attachment site atabout amino acids 239 to 242, and a Ly-6/u-PAR domain at about aminoacids 23 to 36.

Analysis of the amino acid sequence of the full-length PRO1074polypeptide suggests that it possesses significant sequence similarityto beta 1,3-galactosyltransferase, thereby indicating that PRO1074 maybe a novel member of the galactosyltransferase family of proteins.Analysis of the amino acid sequence of the full-length PRO1074polypeptide using the Dayhoff database (version 35.45 SwissProt 35)evidenced homology between the PRO1074 amino acid sequence and thefollowing Dayhoff sequences: AF029792_(—)1, P_R57433, DMU41449_(—)1,AC000348_(—)14, P_R47479, CET09F5_(—)2, CEF14B6_(—)4, CET15D6_(—)5,CEC54C8_(—)4, and CEE03H4_(—)10.

Clone DNA57704-1452 was deposited with the ATCC on Jun. 9, 1998, and isassigned ATCC deposit no. 209953.

Example 59 Isolation of cDNA Clones Encoding Human PRO1005

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of an EST cluster sequence from the LIFESEQ®database, Incyte cluster sequence no. 49243. This EST cluster sequencewas then compared to a variety of expressed sequence tag (EST) databaseswhich included public EST databases (e.g., GenBank) and a proprietaryEST DNA database (LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, Calif.)to identify existing homologies. The homology search was performed usingthe computer program BLAST or BLAST2 (Altshul et al., Methods inEnzymology 266:460–480 (1996)). Those comparisons resulting in a BLASTscore of 70 (or in some cases 90) or greater that did not encode knownproteins were clustered and assembled into a consensus DNA sequence withthe program “phrap” (Phil Green, University of Washington, Seattle,Wash.). The consensus sequence obtained therefrom is herein designatedDNA56380.

In light of an observed sequence homology between the DNA56380 consensussequence and an EST sequence encompassed within the Merck EST clone no.AA256657, the Merck EST clone AA256657 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.138 and is herein designated as DNA57708-1411.

The full length clone shown in FIG. 138 contained a single open readingframe with an apparent translational initiation site at nucleotidepositions 30–32 and ending at the stop codon found at nucleotidepositions 585–587 (FIG. 138; SEQ ID NO:210). The predicted polypeptideprecursor (FIG. 139, SEQ ID NO:211) is 185 amino acids long. PRO1005 hasa calculated molecular weight of approximately 20,331 daltons and anestimated pI of approximately 5.85. Clone DNA57708-1411 was depositedwith the ATCC Jun. 23, 1998, and is assigned ATCC deposit no. 203021.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 139 (SEQ ID NO:211), evidenced some homology between thePRO1005 amino acid sequence and the following Dayhoff sequences:DDU07187_(—)1, DDU87912_(—)1, CELD1007_(—)14, A42239, DDU42597_(—)1,CYAG_DICDI, S50452, MRKC_KLEPN, P-R41998, and XYNA_RUMFL.

Example 60 Isolation of cDNA Clones Encoding Human PRO1073

An initial DNA sequence referred to herein as DNA55938 and shown in FIG.142 (SEQ ID NO:214) was identified using a yeast screen, in a humanSK-Lu-1 adenocarcinoma cell line cDNA library that preferentiallyrepresents the 5′ ends of the primary cDNA clones. DNA55938 was thencompared to ESTs from public databases (e.g., GenBank), and aproprietary EST database (LIFESEQ®, Incyte Pharmaceuticals, Palo Alto,Calif.), using the computer program BLAST or BLAST2 [Altschul et al.,Methods in Enzymology, 266:460–480 (1996)]. The ESTs were clustered andassembled into a consensus DNA sequence using the computer program“phrap” (Phil Green, University of Washington, Seattle, Wash.). Theconsensus sequence obtained is designated herein as DNA56411.

In light of an observed sequence homology between the DNA56411 consensussequence and an EST sequence encompassed within the Merck EST clone no.H86027, the Merck EST clone H86027 was purchased and the cDNA insert wasobtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.140.

The full length DNA57710-1451 clone shown in FIG. 140 contained a singleopen reading frame with an apparent translational initiation site atnucleotide positions 345–347 and ending at the stop codon found atnucleotide positions 1242–1244 (FIG. 140; SEQ ID NO:212). The predictedpolypeptide precursor (FIG. 141. SEQ ID NO:213) is 299 amino acids long.PRO1073 has a calculated molecular weight of approximately 34,689daltons and an estimated pI of approximately 11.49. The PRO1073polypeptide has the following additional features: a signal peptide atabout amino acids 1–31, sequence identity to bZIP transcription factorbasic domain signature at about amino acids, a potential N-glycosylationsite at about amino acids 2–5, and sequence identity with protamine P1proteins at about amino acids 158–183.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST-2 sequence alignment analysis of the full-length sequenceshown in FIG. 141 (SEQ ID NO:213), revealed some sequence identitybetween the PRO1073 amino acid sequence and the following Dayhoffsequences: MMU37351_(—)1, ATAC00250510T9J22.10, S59043, ENXNUPR_(—)1,B47328, SR55_DROME, S26650, SON_HUMAN, VIT2_CHICK, and XLC4SRPRT_(—)1.

Clone DNA57710-1451 was deposited with the ATCC on Jul. 1, 1998 and isassigned ATCC deposit no. 203048.

Example 61 Isolation of cDNA Clones Encoding Human PRO1152

A cDNA clone (DNA57711-1501) encoding a native human PRO1152 polypeptidewas identified by employing a yeast screen, in a human infant brain cDNAlibrary that preferentially represents the 5′ ends of the primary cDNAclones. Specifically, a yeast screen was employed to identify a cDNAdesignated herein as DNA55807 (SEQ ID NO:217; see FIG. 145).

In light of an observed sequence homology between the DNA55807 sequenceand an EST sequence encompassed within the Merck EST clone no. R56756,the Merck EST clone R56756 was purchased and the cDNA insert wasobtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.143.

The full-length DNA57711-1501 clone shown in FIG. 143 contains a singleopen reading frame with an apparent translational initiation site atnucleotide positions 58–60 and ending at the stop codon at nucleotidepositions 1495–1497 (FIG. 143). The predicted polypeptide precursor is479 amino acids long (FIG. 144). The full-length PRO1152 protein shownin FIG. 144 has an estimated molecular weight of about 53,602 daltonsand a pI of about 8.82. Analysis of the full-length PRO1152 sequenceshown in FIG. 144 (SEQ ID NO:216) evidences the presence of thefollowing: a signal peptide from about amino acid 1 to about amino acid28, transmembrane domains from about amino acid 133 to about amino acid155, from about amino acid 168 to about amino acid 187, from about aminoacid 229 to about amino acid 247, from about amino acid 264 to aboutamino acid 285, from about amino acid 309 to about amino acid 330, fromabout amino acid 371 to about amino acid 390 and from about amino acid441 to about amino acid 464, potential N-glycosylation sites from aboutamino acid 34 to about amino acid 37 and from about amino acid 387 toabout amino acid 390 and an amino acid sequence block having homology toa respiratory-chain NADH dehydrogenase subunit from about amino acid 243to about amino acid 287. Clone DNA57711-1501 has been deposited withATCC on Jul. 1, 1998 and is assigned ATCC deposit no. 203047.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST-2 sequence alignment analysis of the full-length sequenceshown in FIG. 144 (SEQ ID NO:216), evidenced significant homologybetween the PRO1152 amino acid sequence and the following Dayhoffsequences: AF052239_(—)1, SYNN9CGA_(—)1, SFCYTB2_(—)1, GEN12507,P_R11769, MTV025_(—)109, C61168, S43171, P_P61689 and P_P61696.

Example 62 Isolation of cDNA Clones Encoding Human PRO1136

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of an EST cluster sequence from the Incytedatabase, designated 109142. This EST cluster sequence was then comparedto a variety of expressed sequence tag (EST) databases which includedpublic EST databases (e.g., GenBank) and a proprietary EST DNA database(Lifeseq®, Incyte Pharmaceuticals, Palo Alto, Calif.) to identifyexisting homologies. The homology search was performed using thecomputer program BLAST or BLAST2 (Altshul et al., Methods in Enzymology266:460–480 (1996)). Those comparisons resulting in a BLAST score of 70(or in some cases 90) or greater that did not encode known proteins wereclustered and assembled into a consensus DNA sequence with the program“phrap” (Phil Green, University of Washington, Seattle, Wash.). Theconsensus sequence obtained therefrom is herein designated DNA56039.

In light of an observed sequence homology between the DNA56039 consensussequence and an EST sequence encompassed within the Merck EST clone no.HSC1NF011, the Merck EST clone HSC1NF011 was purchased and the cDNAinsert was obtained and sequenced. It was found that this insert encodeda full-length protein. The sequence of this cDNA insert is shown in FIG.146 and is herein designated as DNA57827-1493.

Clone DNA57827-1493) contains a single open reading frame with anapparent translational initiation site at nucleotide positions 216–218and ending at the stop codon at nucleotide positions 2112–2114 (FIG.146). The predicted polypeptide precursor is 632 amino acids long (FIG.147). The full-length PRO1136 protein shown in FIG. 147 has an estimatedmolecular weight of about 69,643 daltons and a pI of about 8.5. Analysisof the full-length PRO1136 sequence shown in FIG. 147 (SEQ ID NO:219)evidences the presence of the following: a signal peptide from aboutamino acid 1 to about amino acid 15 and potential N-glycosylation sitesfrom about amino acid 108 to about amino acid 11, from about amino acid157 to about amino acid 160, from about amino acid 289 to about aminoacid 292 and from about amino acid 384 to about amino acid 387. CloneDNA57827-1493 has been deposited with ATCC on Jul. 1, 1998 and isassigned ATCC deposit no. 203045.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 147 (SEQ ID NO:219), evidenced significant homologybetween the PRO1136 amino acid sequence and the following Dayhoffsequences: AF034746_(—)1, AF034745_(—)1, MMAF000168_(—)19, HSMUPP1_(—)1,AF060539_(—)1, SP97_RAT, I38757, MMU93309_(—)1, CEK01A6_(—)4 andHSA224747_(—)1.

Example 63 Isolation of cDNA Clones Encoding Human PRO813

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single Incyte EST cluster sequence (IncyteEST cluster sequence no. 45501. The Incyte EST cluster sequence no.45501 sequence was then compared to a variety of expressed sequence tag(EST) databases which included public EST databases (e.g., GenBank) anda proprietary EST DNA database (LIFESEQ™, Incyte Pharmaceuticals, PaloAlto, Calif.) to identify existing homologies. The homology search wasperformed using the computer program BLAST or BLAST2 (Altshul et al.,Methods in Enzymology 266:460–480 (1996)). Those comparisons resultingin a BLAST score of 70 (or in some cases 90) or greater that did notencode known proteins were clustered and assembled into a consensus DNAsequence with the program “phrap” (Phil Green, University of Washington,Seattle, Wash.). The consensus sequence obtained therefrom is hereindesignated DNA56400.

In light of an observed sequence homology between the DNA56400 consensussequence and an EST sequence encompassed within the Merck EST clone no.T90592, the Merck EST clone T90592 was purchased and the cDNA insert wasobtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.148 and is herein designated DNA57834-1339.

The full length clone shown in FIG. 148 contained a single open readingframe with an apparent translational initiation site at nucleotidepositions 109–111 and ending at the stop codon found at nucleotidepositions 637–639 (FIG. 149; SEQ ID NO:221). The predicted polypeptideprecursor is 176 amino acids long, has a calculated molecular weight ofapproximately 19,616 daltons and an estimated pI of approximately 7.11.Analysis of the full-length PRO813 sequence shown in FIG. 149 (SEQ IDNO:221) evidences the presence of the following: a signal peptide fromabout amino acid 1 to about amino acid 26 and potential N-myristoylationsites from about amino acid 48 to about amino acid 53, from about aminoacid 153 to about amino acid 158, from about amino acid 156 to aboutamino acid 161 and from about amino acid 167 to about amino acid 172.Clone DNA57834-1339 has been deposited with the ATCC on Jun. 9, 1998 andis assigned ATCC deposit no. 209954.

Analysis of the amino acid sequence of the full-length PRO813polypeptide suggests that it possesses sequence similarity to thepulmonary surfactant-associated protein C. More specifically, ananalysis of the Dayhoff database (version 35.45 SwissProt 35) evidencedsome degree of homology between the PRO813 amino acid sequence and thefollowing Dayhoff sequences, PSPC_MUSVI, P_P92071, G02964, P_R65489,P_P82977, P_R84555, S55542, MUSIGHAJ_(—)1 and PH1158.

Example 64 Isolation of cDNA Clones Encoding Human PRO809

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single Incyte EST cluster sequence. TheIncyte EST cluster sequence was then compared to a variety of expressedsequence tag (EST) databases which included public EST databases (e.g.,GenBank) and a proprietary EST DNA database (LIFESEQ™, IncytePharmaceuticals, Palo Alto, Calif.) to identify existing homologies. Thehomology search was performed using the computer program BLAST or BLAST2(Altshul et al., Methods in Enzymology 266:460–480 (1996)). Thosecomparisons resulting in a BLAST score of 70 (or in some cases 90) orgreater that did not encode known proteins were clustered and assembledinto a consensus DNA sequence with the program “phrap” (Phil Green,University of Washington, Seattle, Wash.). The consensus sequenceobtained therefrom is herein designated DNA56418.

In light of an observed sequence homology between the DNA56418 consensussequence and an EST sequence encompassed within the Merck EST clone no.H74302, the Merck EST clone H74302 was purchased and the cDNA insert wasobtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.150 and is herein designated DNA57836-1338.

The entire nucleotide sequence of DNA57836-1338 is shown in FIG. 150(SEQ ID NO:222). Clone DNA57836-1338 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 63–65 and ending at the stop codon at nucleotide positions858–860 of SEQ ID NO:222 (FIG. 150). The predicted polypeptide precursoris 265 amino acids long (FIG. 151). The full-length PRO809 protein shownin FIG. 151 has an estimated molecular weight of about 29,061 daltonsand a pI of about 9.18. FIG. 151 further shows the approximate positionsof the signal peptide and N-glysosylation sites. The correspondingnucleotides can be determined by referencing FIG. 150. CloneDNA57836-1338 has been deposited with ATCC on Jun. 23, 1998. It isunderstood that the deposited clone has the actual nucleic acid sequenceand that the sequences provided herein are based on known sequencingtechniques.

Analysis of the amino acid sequence of the full-length PRO809polypeptide suggests that it possesses some sequence similarity to theheparin sulfate proteoglycan and to endothelial cell adhesionmolecule-1. More specifically, an analysis of the Dayhoff database(version 35.45 SwissProt 35) evidenced sequence identity between thePRO809 amino acid sequence and the following Dayhoff sequences,PGBM_MOUSE, D82082_(—)1 and PW14158.

Example 65 Isolation of cDNA Clones Encoding Human PRO791

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single Incyte EST cluster sequence. TheIncyte EST cluster sequence was then compared to a variety of expressedsequence tag (EST) databases which included public EST databases (e.g.,GenBank) and a proprietary EST DNA database (LIFESEQ™, IncytePharmaceuticals, Palo Alto, Calif.) to identify existing homologies. Thehomology search was performed using the computer program BLAST or BLAST2(Altshul et al., Methods in Enzymology 266:460–480 (1996)). Thosecomparisons resulting in a BLAST score of 70 (or in some cases 90) orgreater that did not encode known proteins were clustered and assembledinto a consensus DNA sequence with the program “phrap” (Phil Green,University of Washington, Seattle, Wash.). The consensus sequenceobtained therefrom is herein designated DNA56429.

In light of an observed sequence homology between the DNA56429 consensussequence and an EST sequence encompassed within the Merck EST clone no.36367, the Merck EST clone 36367 was purchased and the cDNA insert wasobtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.152 and is herein designated DNA57838-1337.

The entire nucleotide sequence of DNA57838-1337 is shown in FIG. 152(SEQ ID NO:224). Clone DNA57838-1337 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 9–11 and ending at the stop codon at nucleotide positions747–749 of SEQ ID NO:224 (FIG. 152). The predicted polypeptide precursoris 246 amino acids long (FIG. 153). The full-length PRO791 protein shownin FIG. 153 has an estimated molecular weight of about 27,368 daltonsand a pI of about 7.45. FIG. 153 also shows the approximate locations ofthe signal peptide, the transmembrane domain, N-glycosylation sites anda region conserved in extracellular proteins. The correspondingnucleotides of one embodiment provided herein can be identified byreferencing FIG. 152. Clone DNA57838-1337 has been deposited with ATCCon Jun. 23, 1998. It is understood that the deposited clone has theactual nucleic acid sequence and that the sequences provided herein arebased on known sequencing techniques.

Analysis of the amino acid sequence of the full-length PRO791polypeptide suggests that it has sequence similarity with MHC-Iantigens, thereby indicating that PRO791 may be related to MHC-Iantigens. More specifically, an analysis of the Dayhoff database(version 35.45 SwissProt 35) evidenced some sequence identity betweenthe PRO791 amino acid sequence and the following Dayhoff sequences,AF034346_(—)1, MMQ1K5_(—)1 and HFE_HUMAN.

Example 66 Isolation of cDNA Clones Encoding Human PRO1004

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single Incyte EST cluster sequence, Incytecluster sequence No. 73681. This EST cluster sequence was then comparedto a variety of expressed sequence tag (EST) databases which includedpublic EST databases (e.g., GenBank) to identify existing homologies.The homology search was performed using the computer program BLAST orBLAST2 (Altshul et al., Methods in Enzymology 266:460–480 (1996)). Thosecomparisons resulting in a BLAST score of 70 (or in some cases 90) orgreater that did not encode known proteins were clustered and assembledinto a consensus DNA sequence with the program “phrap” (Phil Green,Univ. of Washington, Seattle, Wash.). The consensus sequence obtainedtherefrom is herein designated as DNA56516.

In light of an observed sequence homology between the DNA56516 consensussequence and an EST sequence encompassed within the Merck EST clone no.H43837, the Merck EST clone H43837 was purchased and the cDNA insert wasobtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.154.

The full length clone shown in FIG. 154 contained a single open readingframe with an apparent translational initiation site at nucleotidepositions 119–121 and ending at the stop codon at nucleotide positions464–466 (FIG. 154; SEQ ID NO:226). The predicted polypeptide precursoris 115 amino acids long (FIG. 155; SEQ ID NO:227). The full-lengthPRO1004 protein shown in FIG. 155 has an estimated molecular weight ofabout 13,649 daltons and a pI of about 9.58. Analysis of the full-lengthPRO1004 sequence shown in FIG. 155 (SEQ ID NO:227) evidences thepresence of the following features: a signal peptide at about aminoacids 1–24, a microbodies C-terminal targeting signal at about aminoacids 113–115, a potential N-glycosylation site at about amino acids71–74, and a domain having sequence identity with dihydrofolatereductase proteins at about amino acids 22–48.

Analysis of the amino acid sequence of the full-length PRO1004polypeptide using the Dayhoff database (version 35.45 SwissProt 35)evidenced homology between the PRO1004 amino acid sequence and thefollowing Dayhoff sequences: CELR02D3_(—)7, LECI_MOUSE, AF006691_(—)3,SSZ97390_(—)1, SSZ97395_(—)1, and SSZ97400_(—)1.

Clone DNA57844-1410 was deposited with the ATCC on Jun. 23, 1998, and isassigned ATCC deposit no. 203010.

Example 67 Isolation of cDNA Clones Encoding Human PRO1111

An expressed sequence tag (EST) DNA database (LIFESEQ®, IncytePharmaceuticals, Palo Alto, Calif.) was searched and an EST wasidentified which had homology to insulin-like growth factor bindingprotein.

RNA for construction of cDNA libraries was isolated from human fetalbrain. The cDNA libraries used to isolate the cDNA clones encoding humanPRO1111 were constructed by standard methods using commerciallyavailable reagents such as those from Invitrogen, San Diego, Calif. ThecDNA was primed with oligo dT containing a NotI site, linked with bluntto Sa1I hemikinased adaptors, cleaved with NotI, sized appropriately bygel electrophoresis, and cloned in a defined orientation into a suitablecloning vector (such as pRKB or pRKD; pRK5B is a precursor of pRK5D thatdoes not contain the SfiI site; see, Holmes et al., Science,253:1278–1280 (1991)) in the unique XhoI and NotI.

The human fetal brain cDNA libraries (prepared as described above), werescreened by hybridization with a synthetic oligonucleotide probe basedupon the Incyte EST sequence described above:

-   5′-CCACCACCTGGAGGTCCTGCAGTTGGGCAGGAACTCCATCCGGCAGATTG-3′ (SEQ ID    NO:251).

An identified cDNA clone was sequenced in entirety. The entirenucleotide sequence of PRO1111 is shown in FIG. 156 (SEQ ID NO:228).Clone DNA58721-1475 contains a single open reading frame with anapparent translational initiation site at nucleotide positions 57–59 anda stop codon at nucleotide positions 2016–2018 (FIG. 156; SEQ IDNO:228). The predicted polypeptide precursor is 653 amino acids long(FIG. 157). The transmembrane domains are at positions 21–40 (type II)and 528–548. Clone DNA58721-1475 has been deposited with ATCC and isassigned ATCC deposit no.203110. The full-length PRO1111 protein shownin FIG. 157 has an estimated molecular weight of about 72,717 daltonsand a pI of about 6.99.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 157 (SEQ ID NO:229), revealed some sequence identitybetween the PRO1111 amino acid sequence and the following Dayhoffsequences: A58532, D86983_(—)1, RNPLGPV_(—)1, PGS2_HUMAN, AF038127_(—)1,ALS_MOUSE, GPV_HUMAN, PGS2_BOVIN, ALS_PAPPA and I47020.

Example 68 Isolation of cDNA Clones Encoding Human PRO1344

A consensus DNA sequence was assembled relative to other EST sequencesusing phrap as described in Example 1 above. This consensus sequence isherein designated DNA33790. Based on the DNA33790 consensus sequence,oligonucleotides were synthesized: 1) to identify by PCR a cDNA librarythat contained the sequence of interest, and 2) for use as probes toisolate a clone of the full-length coding sequence for PRO1344.

PCR primers (forward and reverse) were synthesized:

forward PCR primer 5′-AGGTTCGTGATGGAGACAACCGCG-3′ (SEQ ID NO:232)reverse PCR primer 5′-TGTCAAGGACGCACTGCCGTCATG-3′ (SEQ ID NO:233)Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the consensus DNA33790 sequence which had the followingnucleotide sequenceHybridization Probe

-   5′-TGGCCAGATCATCAAGCGTGTCTGTGGCAACGAGCGGCCAGCTCCTATCC-3′ (SEQ ID    NO:234)

In order to screen several libraries for a source of a full-lengthclone, DNA from the libraries was screened by PCR amplification with thePCR primer pair identified above. A positive library was then used toisolate clones encoding the PRO1344 gene using the probe oligonucleotideand one of the PCR primers. RNA for construction of the cDNA librarieswas isolated from human fetal kidney tissue.

DNA sequencing of the clones isolated as described above gave thefull-length DNA sequence for PRO1344 (designated herein as DNA58723-1588[FIG. 158, SEQ ID NO:230]); and the derived protein sequence forPRO1344.

The entire nucleotide sequence of DNA58723-1588 is shown in FIG. 158(SEQ ID NO:230). Clone DNA58723-1588 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 26–28 and ending at the stop codon at nucleotide positions2186–2188 (FIG. 158). The predicted polypeptide precursor is 720 aminoacids long (FIG. 159). The full-length PRO1344 protein shown in FIG. 159has an estimated molecular weight of about 80,199 daltons and a pI ofabout 7.77. Analysis of the full-length PRO1344 sequence shown in FIG.159 (SEQ ID NO:231) evidences the presence of the following: a signalpeptide from about amino acid 1 to about amino acid 23, an EGF-likedomain cysteine protein signature sequence from about amino acid 260 toabout amino acid 271, potential N-glycosylation sites from about aminoacid 96 to about amino acid 99, from about amino acid 279 to about aminoacid 282, from about amino acid 316 to about amino acid 319, from aboutamino acid 451 to about amino acid 454 and from about amino acid 614 toabout amino acid 617, an amino acid sequence block having homology toserine proteases, trypsin family from about amino acid 489 to aboutamino acid 505 and a CUB domain protein profile sequence from aboutamino acid 150 to about amino acid 166. Clone DNA58723-1588 has beendeposited with ATCC on Aug. 18, 1998 and is assigned ATCC deposit no.203133.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 159 (SEQ ID NO:231), evidenced significant homologybetween the PRO1344 amino acid sequence and the following Dayhoffsequences: S77063_(—)1, CRAR_MOUSE, P_R74775, P_P90070, P_R09217,P_P70475, HSBMP16_(—)1 and U50330_(—)1.

Example 69 Isolation of cDNA Clones Encoding Human PRO1109

A consensus DNA sequence was assembled relative to other EST sequencesusing phrap as described in Example 1 above. This consensus sequence isherein designated DNA52642. The consensus DNA sequence was obtained byextending using repeated cycles of BLAST and phrap a previously obtainedconsensus sequence as far as possible using the sources of EST sequencesdiscussed above. Based on the DNA52642 consensus sequence,oligonucleotides were synthesized: 1) to identify by PCR a cDNA librarythat contained the sequence of interest, and 2) for use as probes toisolate a clone of the full-length coding sequence for PRO1109.

PCR primers (forward and reverse) were synthesized:

forward PCR primer 5′-CCTTACCTCAGAGGCCAGAGCAAGC-3′ (SEQ ID NO:237)reverse PCR primer 5′-GAGCTTCATCCGTTCTGCGTTCACC-3′ (SEQ ID NO:238)Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the consensus DNA52642 sequence which had the followingnucleotide sequenceHybridization Probe

-   5′-CAGGAATGTAAAGCTTTACAGAGGGTCGCCATCCTCGTTCCCCACC-3′ (SEQ ID NO:239)

In order to screen several libraries for a source of a full-lengthclone, DNA from the libraries was screened by PCR amplification with thePCR primer pair identified above. A positive library was then used toisolate clones encoding the PRO1109 gene using the probe oligonucleotideand one of the PCR primers. RNA for construction of the cDNA librarieswas isolated from human SK-Lu-1 adenocarcinoma cell tissue (LIB247).

DNA sequencing of the clones isolated as described above gave thefull-length DNA sequence for PRO1109 (designated herein as DNA58737-1473[FIG. 160, SEQ ID NO:235]) and the derived protein sequence for PRO1109.

The entire nucleotide sequence of DNA58737-1473 is shown in FIG. 160(SEQ ID NO:235). Clone DNA58737-1473 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 119–120 and ending at the stop codon at nucleotide positions1151–1153 (FIG. 160). The predicted polypeptide precursor is 344 aminoacids long (FIG. 161). The full-length PRO1109 protein shown in FIG. 161has an estimated molecular weight of about 40,041 daltons and a pI ofabout 9.34. Analysis of the full-length PRO1109 sequence shown in FIG.161 (SEQ ID NO:236) evidences the presence of the following: a signalpeptide from about amino acid 1 to about amino acid 27, potentialN-glycosylation sites from about amino acid 4 to about amino acid 7,from about amino acid 220 to about amino acid 223 and from about aminoacid 335 to about amino acid 338 and an amino acid sequence block havinghomology to xylose isomerase proteins from about amino acid 191 to aboutamino acid 201. Clone DNA58737-1473 has been deposited with ATCC on Aug.18, 1998 and is assigned ATCC deposit no. 203136.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 161 (SEQ ID NO:236), evidenced significant homologybetween the PRO1109 amino acid sequence and the following Dayhoffsequences: HSUDPGAL_(—)1, HSUDPB14_(—)1, NALS_BOVIN, HSU10473_(—)1,CEW02B12_(—)11, YNJ4_CAEEL, AE000738_(—)11, CET24D1_(—)1, S48121 andCEGLY9_(—)1.

Example 70 Isolation of cDNA Clones Encoding Human PRO1383

A consensus DNA sequence was assembled relative to other EST sequencesusing phrap as described in Example 1 above. This consensus sequence isherein designated DNA53961. Based on the DNA53961 consensus sequence,oligonucleotides were synthesized: 1) to identify by PCR a cDNA librarythat contained the sequence of interest, and 2) for use as probes toisolate a clone of the full-length coding sequence for PRO1383.

PCR primers (forward and reverse) were synthesized:

forward PCR primer 5′-CATTTCCTTACCCTGGACCCAGCTCC-3′ (SEQ ID NO:242)reverse PCR primer 5′-GAAAGGCCCACAGCACATCTGGCAG-3′ (SEQ ID NO:243)Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the consensus DNA53961 sequence which had the followingnucleotide sequenceHybridization Probe

-   5′-CCACGACCCGAGCAACTTCCTCAAGACCGACTTGTTTCTCTACAGC-3′ (SEQ ID NO:244)

In order to screen several libraries for a source of a full-lengthclone, DNA from the libraries was screened by PCR amplification with thePCR primer pair identified above. A positive library was then used toisolate clones encoding the PRO1383 gene using the probe oligonucleotideand one of the PCR primers. RNA for construction of the cDNA librarieswas isolated from human fetal brain tissue.

DNA sequencing of the clones isolated as described above gave thefull-length DNA sequence for PRO1383 (designated herein as DNA58743-1609[FIG. 162, SEQ ID NO:240]) and the derived protein sequence for PRO1383.

The entire nucleotide sequence of DNA58743-1609 is shown in FIG. 162(SEQ ID NO:240). Clone DNA58743-1609 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 122–124 and ending at the stop codon at nucleotide positions1391–1393 (FIG. 162). The predicted polypeptide precursor is 423 aminoacids long (FIG. 163). The full-length PRO1383 protein shown in FIG. 163has an estimated molecular weight of about 46,989 daltons and a pI ofabout 6.77. Analysis of the full-length PRO1383 sequence shown in FIG.163 (SEQ ID NO:241) evidences the presence of the following: a signalpeptide from about amino acid 1 to about amino acid 24, a transmembranedomain from about amino acid 339 to about amino acid 362, and potentialN-glycosylation sites from about amino acid 34 to about amino acid 37,from about amino acid 58 to about amino acid 61, from about amino acid142 to about amino acid 145, from about amino acid 197 to about aminoacid 200, from about amino acid 300 to about amino acid 303 and fromabout amino acid 364 to about amino acid 367. Clone DNA58743-1609 hasbeen deposited with ATCC on Aug. 25, 1998 and is assigned ATCC depositno. 203154.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 163 (SEQ ID NO:241), evidenced significant homologybetween the PRO1383 amino acid sequence and the following Dayhoffsequences: NMB_HUMAN, QNR_COTJA, P_W38335, P115_CHICK, P_W38164,A45993_(—)1, MMU70209_(—)1, D83704_(—)1 and P_W39176.

Example 71 Isolation of cDNA Clones Encoding Human PRO1003

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single Incyte EST cluster sequencedesignated herein as 43055. This sequence was then compared to a varietyof EST databases which included public EST databases (e.g., GenBank) anda proprietary EST DNA database (LIFESEQ™, Incyte Pharmaceuticals, PaloAlto, Calif.) to identify existing homologies. The homology search wasperformed using the computer program BLAST or BLAST2 (Altshul et al.,Methods in Enzymology 266:460–480 (1996)). Those comparisons resultingin a BLAST score of 70 (or in some cases 90) or greater that did notencode known proteins were clustered and assembled into a consensus DNAsequence with the program “phrap” (Phil Green, University of Washington,Seattle, Wash.). The consensus sequence obtained therefrom is hereindesignated consen01.

In light of an observed sequence homology between the consensus sequenceand an EST sequence encompassed within the Incyte EST clone no. 2849382,the Incyte EST clone 2849382 was purchased and the cDNA insert wasobtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.164.

The entire nucleotide sequence of DNA58846-1409 is shown in FIG. 164(SEQ ID NO:245). Clone DNA58846-1409 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 41–43 and ending at the stop codon at nucleotide positions293–295 (FIG. 164). The predicted polypeptide precursor is 84 aminoacids long (FIG. 165). The full-length PRO1003 protein shown in FIG. 165has an estimated molecular weight of about 9,408 daltons and a pI ofabout 9.28. Analysis of the full-length PRO1003 sequence shown in FIG.165 (SEQ ID NO:246) evidences the presence of a signal peptide at aminoacids 1 to about 24, and a cAMP- and cGMP-dependent protein kinasephosphorylation site at about amino acids 58 to about 61. Analysis ofthe amino acid sequence of the full-length PRO1003 polypeptide using theDayhoff database (version 35.45 SwissProt 35) evidenced homology betweenthe PRO1003 amino acid sequence and the following Dayhoff sequences:AOPCZA363_(—)3, SRTX_ATREN, A48298, MHVJHMS_(—)1, VGL2_CVMJH,DHDHTC2_(—)2, CORT_RAT, TAL6_HUMAN, P_W14123, and DVUFI_(—)2.

Example 72 Isolation of cDNA Clones Encoding Human PRO1108

A consensus DNA sequence was assembled relative to other EST sequencesusing phrap as described in Example 1 above. This consensus sequence isherein designated DNA53237.

In light of an observed sequence homology between the DNA53237 consensussequence and an EST sequence encompassed within the Incyte EST clone no.2379881, the Incyte EST clone 2379881 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.166 and is herein designated DNA58848-1472.

The entire nucleotide sequence of DNA58848-1472 is shown in FIG. 166(SEQ ID NO:247). Clone DNA58848-1472 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 77–79 and ending at the stop codon at nucleotide positions1445–1447 (FIG. 166). The predicted polypeptide precursor is 456 aminoacids long (FIG. 167). The full-length PRO1108 protein shown in FIG. 167has an estimated molecular weight of about 52,071 daltons and a pI ofabout 9.46. Analysis of the full-length PRO1108 sequence shown in FIG.167 (SEQ ID NO:248) evidences the presence of the following:type IItransmembrane domains from about amino acid 22 to about amino acid 42,from about amino acid 156 to about amino acid 176, from about amino acid180 to about amino acid 199 and from about amino acid 369 to about aminoacid 388, potential N-glycosylaion sites from about amino acid 247 toabout amino acid 250, from about amino acid 327 to about amino acid 330,from about amino acid 328 to about amino acid 331 and from about aminoacid 362 to about amino acid 365 and an amino acid block having homologyto ER lumen protein retaining receptor protein from about amino acid 153to about amino acid 190. Clone DNA58848-1472 has been deposited withATCC on Jun. 9, 1998 and is assigned ATCC deposit no. 209955.

Analysis of the amino acid sequence of the full-length PRO1108polypeptide suggests that it possesses significant sequence similarityto the LPAAT protein, thereby indicating that PRO1108 may be a novelLPAAT homolog. More specifically, an analysis of the Dayhoff database(version 35.45 SwissProt 35) evidenced significant homology between thePRO1108 amino acid sequence and the following Dayhoff sequences,AF015811_(—)1, CER07E3_(—)2, YL35_CAEEL, S73863, CEF59F4_(—)4, P_W06422,MMU41736_(—)1, MTV008_(—)39, P_R99248 and Y67_BPT7.

Example 73 Isolation of cDNA Clones Encoding Human PRO1137

The extracellular domain (ECD) sequences (including the secretionsignal, if any) of from about 950 known secreted proteins from theSwiss-Prot public protein database were used to search expressedsequence tag (EST) databases. The EST databases included public ESTdatabases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ™,Incyte Pharmaceuticals, Palo Alto, Calif.). The search was performedusing the computer program BLAST or BLAST2 (Altshul et al., Methods inEnzymology 266:460–480 (1996)) as a comparison of the ECD proteinsequences to a 6 frame translation of the EST sequence. Using thisprocedure, Incyte EST No. 3459449, also referred to herein as “DNA7108”,was identified as an EST having a BLAST score of 70 or greater that didnot encode a known protein.

A consensus DNA sequence was assembled relative to the DNA7108 sequenceand other ESTs using repeated cycles of BLAST and the program “phrap”(Phil Green, Univ. of Washington, Seattle, Wash.). The consensussequence obtained therefrom is referred to herein as DNA53952.

In light of an observed sequence homology between the DNA53952 consensussequence and an EST sequence encompassed within the Incyte EST clone no.3663102, the Incyte EST clone 3663102 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.168.

The entire nucleotide sequence of DNA58849-1494 is shown in FIG. 168(SEQ ID NO:249). Clone DNA58849-1494 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 77–79 and ending at the stop codon at nucleotide positions797–799 (FIG. 168). The predicted polypeptide precursor is 240 aminoacids long (FIG. 169). The full-length PRO1137 protein shown in FIG. 169has an estimated molecular weight of about 26,064 daltons and a pI ofabout 8.65. Analysis of the full-length PRO1137 sequence shown in FIG.169 (SEQ ID NO:250) evidences the presence of a signal peptide at aboutamino acids 1 to 14 and a potential N-glycosylation site at about aminoacids 101–105.

Analysis of the amino acid sequence of the full-length PRO1137polypeptide suggests that it possesses significant sequence similarityto ribosyltransferase thereby indicating that PRO1137 may be a novelmember of the ribosyltransferase family of proteins. Analysis of theamino acid sequence of the full-length PRO1137 polypeptide using theDayhoff database (version 35.45 SwissProt 35) evidenced homology betweenthe PRO1137 amino acid sequence and the following Dayhoff sequences:MMART5_(—)1, NARG_MOUSE, GEN11909, GEN13794, GEN14406, MMRNART62_(—)1,and P_R41876.

Example 74 Isolation of cDNA Clones Encoding Human PRO1138

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single Incyte EST sequence, Incyte clustersequence no. 165212. This cluster sequence was then compared to avariety of expressed sequence tag (EST) databases which included publicEST databases (e.g., GenBank) and a proprietary EST DNA database(LIFESEQ™, Incyte Pharmaceuticals, Palo Alto, Calif.) to identifyexisting homologies. The homology search was performed using thecomputer program BLAST or BLAST2 (Altshul et al., Methods in Enzymology266:460–480 (1996)). Those comparisons resulting in a BLAST score of 70(or in some cases 90) or greater that did not encode known proteins wereclustered and assembled into a consensus DNA sequence with the program“phrap” (Phil Green, University of Washington, Seattle, Wash.). Theconsensus sequence obtained therefrom is herein designated as DNA54224.The assembly included a proprietary Genentech EST designated herein asDNA49140 (FIG. 172; SEQ ID NO:254).

In light of an observed sequence homology between the DNA54224 consensussequence and an EST sequence encompassed within the Incyte EST clone no.3836613, the Incyte EST clone 3836613 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.170 and is the full-length DNA sequence for PRO1138. Clone DNA58850-1495was deposited with the ATCC on Jun. 9, 1998, and is assigned ATCCdeposit no. 209956.

The entire nucleotide sequence of DNA58850-1495 is shown in FIG. 170(SEQ ID NO:252). Clone DNA58850-1495 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 38–40 and ending at the stop codon at nucleotide positions1043–1045 (FIG. 170). The predicted polypeptide precursor is 335 aminoacids long (FIG. 171). The full-length PRO1138 protein shown in FIG. 171has an estimated molecular weight of about 37,421 Daltons and a pI ofabout 6.36. Analysis of the full-length PRO1138 sequence shown in FIG.171 (SEQ ID NO:253) evidences the presence of the following features: asignal peptide at about amino acid 1 to about amino acid 22; atransmembrane domain at about amino acids 224 to about 250; a leucinezipper pattern at about amino acids 229 to about 250; and potentialN-glycosylation sites at about amino acids 98–101, 142–145, 148–151,172–175, 176–179, 204–207, and 291–295.

Analysis of the amino acid sequence of the full-length PRO1138polypeptide suggests that it possesses significant sequence similarityto the CD84, thereby indicating that PRO1138 may be a novel member ofthe Ig superfamily of polypeptides. More particularly, analysis of theamino acid sequence of the full-length PRO1138 polypeptide using theDayhoff database (version 35.45 SwissProt 35) evidenced homology betweenthe PRO1138 amino acid sequence and the following Dayhoff sequences:HSU82988_(—)1, HUMLY9_(—)1, P_R97631, P_R97628, P_R97629, P_R97630,CD48_RAT, CD2_HUMAN, P_P93996, and HUMBGP_(—)1.

Clone DNA58850-1495 was deposited with ATCC on Jun. 9, 1998, and isassigned ATCC deposit no. 209956.

Example 75 Isolation of cDNA Clones Encoding Human PRO1054

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of an EST cluster sequence from the Incytedatabase, designated 66212. This EST cluster sequence was then comparedto a variety of expressed sequence tag (EST) databases which includedpublic EST databases (e.g., GenBank) and a proprietary EST DNA database(LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, Calif.) to identifyexisting homologies. The homology search was performed using thecomputer program BLAST or BLAST2 (Altshul et al., Methods in Enzymology266:460–480 (1996)). Those comparisons resulting in a BLAST score of 70(or in some cases 90) or greater that did not encode known proteins wereclustered and assembled into a consensus DNA sequence with the program“phrap” (Phil Green, University of Washington, Seattle, Wash.). Theconsensus sequence obtained therefrom is herein designated DNA55722.

In light of an observed sequence homology between the DNA55722 consensussequence and an EST sequence encompassed within the Incyte EST clone no.319751, the Incyte EST clone 319751 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.173 and is herein designated as DNA58853-1423.

Clone DNA58853-1423 contains a single open reading frame with anapparent translational initiation site at nucleotide positions 46–48 andending at the stop codon at nucleotide positions 586–588 (FIG. 173). Thepredicted polypeptide precursor is 180 amino acids long (FIG. 174). Thefull-length PRO1054 protein shown in FIG. 174 has an estimated molecularweight of about 20,638 daltons and a pI of about 5.0. Analysis of thefull-length PRO1054 sequence shown in FIG. 174 (SEQ ID NO:256) evidencesthe presence of the following: a signal peptide from about amino acid 1to about amino acid 18, a leucine zipper pattern from about amino acid155 to about amino acid 176 and amino acid sequence blocks havinghomology to lipocalin proteins from about amino acid 27 to about aminoacid 38 and from, about amino acid 110 to about amino acid 120. CloneDNA58853-1423 has been deposited with ATCC on Jun. 23, 1998 and isassigned ATCC deposit no. 203016.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 174 (SEQ ID NO:256), evidenced significant homologybetween the PRO1054 amino acid sequence and the following Dayhoffsequences: MUP1_MOUSE, MUP6_MOUSE, MUP2_MOUSE, MUP8_MOUSE, MUP5_MOUSE,MUP4_MOUSE, S10124, MUPM_MOUSE, MUP_RAT and ECU70823_(—)1.

Example 76 Isolation of cDNA Clones Encoding Human PRO994

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of an EST cluster sequence from the Incytedatabase, designated 157555. This EST cluster sequence was then comparedto a variety of expressed sequence tag (EST) databases which includedpublic EST databases (e.g., GenBank) and a proprietary EST DNA database(LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, Calif.) to identifyexisting homologies. The homology search was performed using thecomputer program BLAST or BLAST2 (Altshul et al., Methods in Enzymology266:460–480 (1996)). Those comparisons resulting in a BLAST score of 70(or in some cases 90) or greater that did not encode known proteins wereclustered and assembled into a consensus DNA sequence with the program“phrap” (Phil Green, University of Washington, Seattle, Wash.). Theconsensus sequence obtained therefrom is herein designated DNA55728.

In light of an observed sequence homology between the DNA55728 consensussequence and an EST sequence encompassed within the Incyte EST clone no.2860366, the Incyte EST clone 2860366 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.175 and is herein designated as DNA588553-1422.

Clone DNA588553-1422 contains a single open reading frame with anapparent translational initiation site at nucleotide positions 31–33 andending at the stop codon at nucleotide positions 718–720 (FIG. 175). Thepredicted polypeptide precursor is 229 amino acids long (FIG. 176). Thefull-length PRO994 protein shown in FIG. 176 has an estimated molecularweight of about 25,109 daltons and a pI of about 6.83. Analysis of thefull-length PRO994 sequence shown in FIG. 176 (SEQ ID NO:258) evidencesthe presence of the following: transmembrane domains from about aminoacid 10 to about amino acid 31, from about amino acid 50 to about aminoacid 72, from about amino acid 87 to about amino acid 110 and from aboutamino acid 191 to about amino acid 213, potential N-glycosylation sitesfrom about amino acid 80 to about amino acid 83, from about amino acid132 to about amino acid 135, from about amino acid 148 to about aminoacid 151 and from about amino acid 163 to about amino acid 166 and anamino acid block having homology to TNFR/NGFR cysteine-rich regionproteins from about amino acid 4 to about amino acid 11. CloneDNA588553-1422 has been deposited with ATCC on Jun. 23, 1998 and isassigned ATCC deposit no. 203018.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 176 (SEQ ID NO:258), evidenced significant homologybetween the PRO994 amino acid sequence and the following Dayhoffsequences: AF027204_(—)1, TAL6_HUMAN, ILT4_HUMAN, JC6205, MMU57570_(—)1,S40363, ETU56093_(—)1, S42858, P_R66849 and P_R74751.

Example 77 Isolation of cDNA Clones Encoding Human PRO812

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of an EST cluster sequence from the Incytedatabase, designated 170079. This EST cluster sequence was then comparedto a variety of expressed sequence tag (EST) databases which includedpublic EST databases (e.g., GenBank) and a proprietary EST DNA database(Lifeseq®, Incyte Pharmaceuticals, Palo Alto, Calif.) to identifyexisting homologies. The homology search was performed using thecomputer program BLAST or BLAST2 (Altshul et al., Methods in Enzymology266:460–480 (1996)). Those comparisons resulting in a BLAST score of 70(or in some cases 90) or greater that did not encode known proteins wereclustered and assembled into a consensus DNA sequence with the program“phrap” (Phil Green, University of Washington, Seattle, Wash.). Theconsensus sequence obtained therefrom is herein designated as DNA55721.

In light of an observed sequence homology between the DNA55721 consensussequence and an EST sequence encompassed within the Incyte EST clone no.388964, the Incyte EST clone 388964 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.177 and is herein designated as DNA59205-1421.

Clone DNA59205-1421 contains a single open reading frame with anapparent translational initiation site at nucleotide positions 55–57 andending at the stop codon at nucleotide positions 304–306 (FIG. 177). Thepredicted polypeptide precursor is 83 amino acids long (FIG. 178). Thefull-length PRO812 protein shown in FIG. 178 has an estimated molecularweight of about 9,201 daltons and a pI of about 9.3. Analysis of thefull-length PRO812 sequence shown in FIG. 178 (SEQ ID NO:260) evidencesthe presence of the following: a signal peptide from about amino acid 1to about amino acid 15, a cAMP- and cGMP-dependent protein kinasephosphorylation site from about amino acid 73 to about amino acid 76 andprotein kinase C phosphorylation sites from about amino acid 70 to aboutamino acid 72 and from about amino acid 76 to about amino acid 78. CloneDNA59205-1421 has been deposited with ATCC on Jun. 23, 1998 and isassigned ATCC deposit no. 203009.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 178 (SEQ ID NO:260), evidenced significant homologybetween the PRO812 amino acid sequence and the following Dayhoffsequences: P_W35802, P_W35803, PSC1_RAT, S68231, GEN13917, PSC2_RAT,CC10_HUMAN, UTER_RABIT, AF008595_(—)1 and A56413.

Example 78 Isolation of cDNA Clones Encoding Human PRO1069

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single Incyte EST sequence designated hereinas 100727. This sequence was then compared to a proprietary EST DNAdatabase (LIFESEQ™, Incyte Pharmaceuticals, Palo Alto, Calif.) toidentify existing homologies. The homology search was performed usingthe computer program BLAST or BLAST2 (Altshul et al., Methods inEnzymology 266:460–480 (1996)). Those comparisons resulting in a BLASTscore of 70 (or in some cases 90) or greater that did not encode knownproteins were clustered and assembled into a consensus DNA sequence withthe program “phrap” (Phil Green, Univ. of Washington, Seattle, Wash.).The consensus sequence obtained therefrom is herein designated DNA56001.

In light of an observed sequence homology between the DNA56001 consensussequence and an EST sequence encompassed within the Incyte EST clone no.3533881, the Incyte EST clone 3533881 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.179 and is the full-length DNA sequence for PRO1069. Clone DNA59211-1450was deposited with the ATCC on Jun. 9, 1998, and is assigned ATCCdeposit no. 209960.

The entire nucleotide sequence of DNA59211-1450 is shown in FIG. 179(SEQ ID NO:261). Clone DNA59211-1450 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 197–199 and ending at the stop codon at nucleotide positions464–466. The predicted polypeptide precursor is 89 amino acids long(FIG. 180). The full-length PRO1069 protein shown in FIG. 180 has anestimated molecular weight of about 9,433 daltons and a pI of about8.21. Analysis of the full-length PRO1069 sequence shown in FIG. 180(SEQ ID NO:262) evidences the presence of the following features: asignal peptide sequence at amino acid 1 to about 16; a transmembranedomain at about amino acids 36 to about 59; potential N-myristoylationsites at about amino acids 41–46, 45–50, and 84–89; and homology withextracellular proteins SCP/Tpx-1/Ag5/PR-1/Sc7 at about amino acids 54 toabout 66.

Analysis of the amino acid sequence of the full-length PRO1069polypeptide suggests that it possesses significant sequence similarityto CHIF, thereby indicating that PRO1069 may be a member of the CHIFfamily of polypeptides. More particularly, analysis of the amino acidsequence of the full-length PRO1069 polypeptide using the Dayhoffdatabase (version 35.45 SwissProt 35) evidenced homology between thePRO1069 amino acid sequence and the following Dayhoff sequences:CHIF_RAT, A55571, PLM_HUMAN, A40533, ATNG_BOVIN, RIC_MOUSE, PETD_SYNY3,VTB1_XENLA, A05009, and S75086.

Clone DNA59211-1450 was deposited with the ATCC on Jun. 9, 1998, and isassigned ATCC deposit no. 209960.

Example 79 Isolation of cDNA Clones Encoding Human PRO1129

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single Incyte EST cluster sequencedesignated herein as 98833. The Incyte EST cluster sequence no. 98833sequence was then compared to a variety of expressed sequence tag (EST)databases which included public EST databases (e.g., GenBank) and aproprietary EST DNA database (LIFESEQ™, Incyte Pharmaceuticals, PaloAlto, Calif.) to identify existing homologies. The homology search wasperformed using the computer program BLAST or BLAST2 (Altshul et al.,Methods in Enzymology 266:460480 (1996)). Those comparisons resulting ina BLAST score of 70 (or in some cases 90) or greater that did not encodeknown proteins were clustered and assembled into a consensus DNAsequence with the program “phrap” (Phil Green, University of Washington,Seattle, Wash.). The consensus sequence obtained therefrom is hereindesignated DNA56038.

In light of an observed sequence homology between the DNA56038 consensussequence and an EST sequence encompassed within the Incyte EST clone no.1335241, the Incyte EST clone 1335241 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.181 and is herein designated DNA59213-1487.

The full length clone shown in FIG. 181 contained a single open readingframe with an apparent translational initiation site at nucleotidepositions 42–44 and ending at the stop codon found at nucleotidepositions 1614–1616 (FIG. 181; SEQ ID NO:263). The predicted polypeptideprecursor is 524 amino acids long, has a calculated molecular weight ofapproximately 60,310 daltons and an estimated pI of approximately 7.46.Analysis of the full-length PRO1129 sequence shown in FIG. 182 (SEQ IDNO:264) evidences the presence of the following: type II transmembranedomains from about amino acid 13 to about amino acid 32 and from aboutamino acid 77 to about amino acid 102, a cytochrome P-450 cysteineheme-iron ligand signature sequence from about amino acid 461 to aboutamino acid 470 and potential N-glycosylation sites from about amino acid112 to about amino acid 115 and from about amino acid 168 to about aminoacid 171. Clone DNA59213-1487 has been deposited with the ATCC on Jun.9, 1998 and is assigned ATCC deposit no. 209959.

Analysis of the amino acid sequence of the full-length PRO1129polypeptide suggests that it possesses sequence similarity to thecytochrome P-450 family of proteins. More specifically, an analysis ofthe Dayhoff database (version 35.45 SwissProt 35) evidenced some degreeof homology between the PRO1129 amino acid sequence and the followingDayhoff sequences, AC004523_(—)1, S45702, AF054821_(—)1 and I53015.

Example 80 Isolation of cDNA Clones Encoding Human PRO1068

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of an EST cluster sequence from the LIFESEQ®database, designated Incyte cluster no. 141736. This EST clustersequence was then compared to a variety of expressed sequence tag (EST)databases which included public EST databases (e.g., GenBank) and aproprietary EST DNA database (LIFESEQ®, Incyte Pharmaceuticals, PaloAlto, Calif.) to identify existing homologies. One or more of the ESTswas derived from a human mast cell line from a patient with mast cellleukemia. The homology search was performed using the computer programBLAST or BLAST2 (Altshul et al., Methods in Enzymology 266:460–480(1996)). Those comparisons resulting in a BLAST score of 70 (or in somecases 90) or greater that did not encode known proteins were clusteredand assembled into a consensus DNA sequence with the program “phrap”(Phil Green, University of Washington, Seattle, Wash.). The consensussequence obtained therefrom is herein designated DNA56094.

In light of an observed sequence homology between the DNA56094 consensussequence and an EST sequence encompassed within the Incyte EST clone no.004974, the Incyte EST clone 004974 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.183 and is herein designated as DNA59214-1449 (SEQ ID NO:265).

The full length clone shown in FIG. 183 contained a single open readingframe with an apparent translational initiation site at nucleotidepositions 42–44 and ending at the stop codon found at nucleotidepositions 414–416 (FIG. 183; SEQ ID NO:265). The predicted polypeptideprecursor (FIG. 184, SEQ ID NO:266) is 124 amino acids long. PRO1068 hasa calculated molecular weight of approximately 14,284 daltons and anestimated pI of approximately 8.14. The PRO1068 polypeptide has thefollowing additional features: a signal peptide sequence at about aminoacids 1–20, a urotensin II signature sequence at about amino acids118–123, a cell attachment sequence at about amino acids 64–66, and apotential cAMP- and cGMP-dependent protein kinase phosphorylation siteat about amino acids 112–115.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 184 (SEQ ID NO:266), revealed homology between the PRO1068amino acid sequence and the following Dayhoff sequences: HALBOP_(—)1,MTV043_(—)36, I50498, and P_R78445.

Clone DNA59214-1449 was deposited with the ATCC on Jul. 1, 1998 and isassigned ATCC deposit no.203046.

Example 81 Isolation of cDNA Clones Encoding Human PRO1066

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single Incyte EST cluster sequencedesignated herein as 79066. The Incyte EST cluster sequence no. 79066sequence was then compared to a variety of expressed sequence tag (EST)databases which included public EST databases (e.g., GenBank) and aproprietary EST DNA database (LIFESEQ™, Incyte Pharmaceuticals, PaloAlto, Calif.) to identify existing homologies. The homology search wasperformed using the computer program BLAST or BLAST2 (Altshul et al.,Methods in Enzymology 266:460–480 (1996)). Those comparisons resultingin a BLAST score of 70 (or in some cases 90) or greater that did notencode known proteins were clustered and assembled into a consensus DNAsequence with the program “phrap” (Phil Green, University of Washington,Seattle, Wash.). The consensus sequence obtained therefrom is hereindesignated DNA56121.

In light of an observed sequence homology between the DNA56121 consensussequence and an EST sequence encompassed within the Incyte EST clone no.1515315, the Incyte EST clone 1515315 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.185 and is herein designated DNA59215-1425.

The full length clone shown in FIG. 185 contained a single open readingframe with an apparent translational initiation site at nucleotidepositions 176–178 and ending at the stop codon found at nucleotidepositions 527–529 (FIG. 185; SEQ ID NO:267). The predicted polypeptideprecursor is 117 amino acids long, has a calculated molecular weight ofapproximately 12,911 daltons and an estimated pI of approximately 5.46.Analysis of the full-length PRO1066 sequence shown in FIG. 186 (SEQ IDNO:268) evidences the presence of the following: a signal peptide fromabout amino acid 1 to about amino acid 23, a cAMP- and cGMP-dependentprotein kinase phosphorylation site from about amino acid 38 to aboutamino acid 41 and potential N-myristoylation sites from about amino acid5 to about amino acid 10, from about amino acid 63 to about amino acid68 and from about amino acid 83 to about amino acid 88. Clone UNQ524(DNA59215-1425) has been deposited with the ATCC on Jun. 9, 1998 and isassigned ATCC deposit no. 209961.

Analysis of the amino acid sequence of the full-length PRO1066polypeptide suggests that it does not possess significant sequencesimilarity to any known human protein. However, an analysis of theDayhoff database (version 35.45 SwissProt 35) evidenced some degree ofhomology between the PRO1066 amino acid sequence and the followingDayhoff sequences, MOTI_HUMAN, AF025667_(—)1, MTCY19H9_(—)8 andRABIGKCH_(—)1.

Example 82 Isolation of cDNA Clones Encoding Human PRO1184

Use of the signal sequence algorithm described in Example 3 on ESTs froman Incyte database allowed identification a candidate sequencedesignated herein as DNA56375. This sequence was then compared to avariety of expressed sequence tag (EST) databases which included publicEST databases (e.g., GenBank) and a proprietary EST DNA database(LIFESEQ™, Incyte Pharmaceuticals, Palo Alto, Calif.) to identifyexisting homologies. The homology search was performed using thecomputer program BLAST or BLAST2 (Altshul et al., Methods in Enzymology266:460–480 (1996)). Those comparisons resulting in a BLAST score of 70(or in some cases 90) or greater that did not encode known proteins wereclustered and assembled into a consensus DNA sequence with the program“phrap” (Phil Green, University of Washington, Seattle, Wash.). Theconsensus sequence obtained therefrom is herein designated DNA56375.

In light of an observed sequence homology between the DNA56375 consensussequence and an EST sequence encompassed within the Incyte EST clone no.1428374, the Incyte EST clone 1428374 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.187.

The full length clone shown in FIG. 187 contained a single open readingframe with an apparent translational initiation site at nucleotidepositions 106–108 and ending at the stop codon found at nucleotidepositions 532–534 (FIG. 187; SEQ ID NO:269). The predicted polypeptideprecursor is 142 amino acids long, has a calculated molecular weight ofapproximately 15,690 daltons and an estimated pI of approximately 9.64.Analysis of the full-length PRO1184 sequence shown in FIG. 188 (SEQ IDNO:270) evidences the presence of a signal peptide at about amino acids1–38. Clone DNA59220-1514 has been deposited with the ATCC on Jun. 9,1998. It is understood that the deposited clone has the actual sequencesand that representations are presented herein.

Analysis of the amino acid sequence of the full-length PRO1184polypeptide suggests that it possesses some sequence identity with aprotein called TIM from Drosophila virilis, designated “DVTIMS02_(—)1”in the Dayhoff data base, (version 35.45 SwissProt 35). Other Dayhoffdatabase (version 35.45 SwissProt 35) sequences having some degree ofsequence identity with PRO1184 include: WIS1_SCHPO, F002186_(—)1,ATAC00239124 and MSAIPRP_(—)1.

Example 83 Isolation of cDNA Clones Encoding Human PRO1360

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of an EST sequence from an Incyte database,designated DNA10572. This EST sequence was then compared to a variety ofexpressed sequence tag (EST) databases which included public ESTdatabases (e.g., GenBank, Merck/Wash. U.) and a proprietary EST DNAdatabase (LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, Calif.) toidentify existing homologies. The homology search was performed usingthe computer program BLAST or BLAST2 (Altshul et al., Methods inEnzymology 266:460–480 (1996)). Those comparisons resulting in a BLASTscore of 70 (or in some cases 90) or greater that did not encode knownproteins were clustered and assembled into a consensus DNA sequence withthe program “phrap” (Phil Green, University of Washington, Seattle,Wash.). The consensus sequence obtained therefrom is herein designatedDNA57314.

In light of an observed sequence homology between the DNA57314 consensussequence and an EST sequence encompassed within the Merck EST clone no.AA406443, the Merck EST clone AA406443 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.189 and is herein designated as DNA59488-1603.

The full length clone shown in FIG. 189 contained a single open readingframe with an apparent translational initiation site at nucleotidepositions 54–56 and ending at the stop codon found at nucleotidepositions 909–911 (FIG. 189; SEQ ID NO:271). The predicted polypeptideprecursor (FIG. 190, SEQ ID NO:272) is 285 amino acids long. PRO1360 hasa calculated molecular weight of approximately 31,433 daltons and anestimated pI of approximately 7.32. Clone DNA59488-1603 was depositedwith the ATCC on Aug. 25, 1998 and is assigned ATCC deposit no. 203157.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 190 (SEQ ID NO:272), revealed sequence identity betweenthe PRO1360 amino acid sequence and the following Dayhoff sequences:UN51_CAEEL, YD4B_SCHPO, AF000634_(—)1, GFO_ZYMMO, YE1J_SCHPO,D86566_(—)1, ZMGFO_(—)1, S76976, PPSA_SYNY3, and CEF28B1_(—)4.

Example 84 Isolation of cDNA Clones Encoding Human PRO1029

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of an EST cluster sequence from the Incytedatabase, designated 18763. This EST cluster sequence was then comparedto a variety of expressed sequence tag (EST) databases which includedpublic EST databases (e.g., GenBank) and a proprietary EST DNA database(LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, Calif.) to identifyexisting homologies. The homology search was performed using thecomputer program BLAST or BLAST2 (Altshul et al., Methods in Enzymology266:460–480 (1996)). Those comparisons resulting in a BLAST score of 70(or in some cases 90) or greater that did not encode known proteins wereclustered and assembled into a consensus DNA sequence with the program“phrap” (Phil Green, University of Washington, Seattle, Wash.). Theconsensus sequence obtained therefrom is herein designated DNA57854.

In light of an observed sequence homology between the DNA57854 consensussequence and an EST sequence encompassed within the Merck EST clone no.T98880, the Merck EST clone T98880 was purchased and the cDNA insert wasobtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.191 and is herein designated as DNA59493-1420.

Clone DNA59493-1420 contains a single open reading frame with anapparent translational initiation site at nucleotide positions 39–41 andending at the stop codon at nucleotide positions 297–299 (FIG. 191). Thepredicted polypeptide precursor is 86 amino acids long (FIG. 192). Thefull-length PRO1029 protein shown in FIG. 192 has an estimated molecularweight of about 9,548 daltons and a pI of about 8.52. Analysis of thefull-length PRO1029 sequence shown in FIG. 192 (SEQ ID NO:274) evidencesthe presence of the following: a signal peptide from about amino acid 1to about amino acid 19, an amino acid block having homology to bacterialrhodopsins retinal binding site protein from about amino acid 50 toabout amino acid 61, a prenyl group binding site from about amino acid83 to about amino acid 86 and a potential N-glycosylation site fromabout amino acid 45 to about amino acid 48. Clone DNA59493-1420 has beendeposited with ATCC on Jul. 1, 1998 and is assigned ATCC deposit no.203050.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 192 (SEQ ID NO:274), evidenced significant homologybetween the PRO1029 amino acid sequence and the following Dayhoffsequences: S66088, AF031815_(—)1, MM4A6L_(—)1, PSEIS52a-1, S17699 andP_R63635.

Example 85 Isolation of cDNA Clones Encoding Human PRO1139

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of an EST cluster sequence from the Incytedatabase, designated 4461. This EST cluster sequence was then comparedto a variety of expressed sequence tag (EST) databases which includedpublic EST databases (e.g., GenBank) and a proprietary EST DNA database(LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, Calif.) to identifyexisting homologies. The homology search was performed using thecomputer program BLAST or BLAST2 (Altshul et al., Methods in Enzymology266:460–480 (1996)). Those comparisons resulting in a BLAST score of 70(or in some cases 90) or greater that did not encode known proteins wereclustered and assembled into a consensus DNA sequence with the program“phrap” (Phil Green, University of Washington, Seattle, Wash.). Theconsensus sequence obtained therefrom is herein designated DNA57312.

The DNA57312 consensus sequence included a 172 nucleotides long publicEST (T62095, Merck/University of Washington public database). This ESTclone, identified herein as a putative protein coding sequence, waspurchased from Merck, and sequenced to provide the coding sequence ofPRO1139 (FIG. 193). As noted before, the deduced amino acid sequence ofDNA59497-1496 shows a significant sequence identity with the deducedamino acid sequence of HSOBRGRP_(—)1. The full-length protein (FIG. 194)contains a putative signal peptide between amino acid residues 1 andabout 28, and three putative transmembrane domains (approximate aminoacid residues 33–52, 71–89, 98–120).

Example 86 Isolation of cDNA Clones Encoding Human PRO1309

An expressed sequence tag (EST) DNA database (LIFESEQ®, IncytePharmaceuticals, Palo Alto, Calif.) was searched and an EST wasidentified which showed homology to SLIT.

RNA for construction of cDNA libraries was isolated from human fetalbrain tissue. The cDNA libraries used to isolate the cDNA clonesencoding human PRO1309 were constructed by standard methods usingcommercially available reagents such as those from Invitrogen, SanDiego, Calif. The cDNA was primed with oligo dT containing a NotI site,linked with blunt to Sa1I hemikinased adaptors, cleaved with NotI, sizedappropriately by gel electrophoresis, and cloned in a definedorientation into a suitable cloning vector (such as pRKB or pRKD; pRK5Bis a precursor of pRK5D that does not contain the SfiI site; see, Holmeset al., Science, 253:1278–1280 (1991)) in the unique XhoI and NotI.

The cDNA libraries (prepared as described above), were screened byhybridization with a synthetic oligonucleotide probe derived from theabove described Incyte EST sequence:

-   5′-TCCGTGCAGGGGGACGCCTTTCAGAAACTGCGCCGAGTTAAGGAAC-3′ (SEQ ID    NO:279).

A cDNA clone was isolated and sequenced in entirety. The entirenucleotide sequence of DNA59588-1571 is shown in FIG. 195 (SEQ IDNO:277). Clone DNA59588-1571 contains a single open reading frame withan apparent translational initiation site at nucleotide positions720–722 and a stop codon at nucleotide positions 2286–2288 (FIG. 195;SEQ ID NO:277). The predicted polypeptide precursor is 522 amino acidslong. The signal peptide is approximately at 1–34 and the transmembranedomain is at approximately 428–450 of SEQ ID NO:278. Clone DNA59588-1571has been deposited with ATCC and is assigned ATCC deposit no. 203106.The full-length PRO1309 protein shown in FIG. 196 has an estimatedmolecular weight of about 58,614 daltons and a pI of about 7.42.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 196 (SEQ ID NO:278), revealed sequence identity betweenthe PRO1309 amino acid sequence and the following Dayhoff sequences:AB007876_(—)1, GPV_MOUSE, ALS_RAT, P_R85889, LUM_CHICK, AB014462_(—)1,PGS1_CANFA, CEM88_(—)7, A58532 and GEN11209.

Example 87 Isolation of cDNA Clones Encoding Human PRO1028

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a certain EST cluster sequence from the Incytedatabase. This EST cluster sequence was then compared to a variety ofexpressed sequence tag (EST) databases which included public ESTdatabases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ®,Incyte Pharmaceuticals, Palo Alto, Calif.) to identify existinghomologies. The homology search was performed using the computer programBLAST or BLAST2 (Altshul et al., Methods in Enzymology 266:460–480(1996)). Those comparisons resulting in a BLAST score of 70 (or in somecases 90) or greater that did not encode known proteins were clusteredand assembled into a consensus DNA sequence with the program “phrap”(Phil Green, University of Washington, Seattle, Wash.). The consensussequence obtained therefrom is herein designated DNA59603.

In light of an observed sequence homology between the DNA59603 sequenceand an EST sequence contained within Incyte EST clone no. 1497725, theIncyte EST clone no. 1497725 was purchased and the cDNA insert wasobtained and sequenced. It was found that the insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.197 and is herein designated as DNA59603-1419.

The entire nucleotide sequence of DNA59603-1419 is shown in FIG. 197(SEQ ID NO:280). Clone DNA59603-1419 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 21–23 and ending at the stop codon at nucleotide positions612–614 (FIG. 197). The predicted polypeptide precursor is 197 aminoacids long (FIG. 198). The full-length PRO1028 protein shown in FIG. 198has an estimated molecular weight of about 20,832 daltons and a pI ofabout 8.74. Clone DNA59603-1419 has been deposited with the ATCC.Regarding the sequence, it is understood that the deposited clonecontains the correct sequence, and the sequences provided herein arebased on known sequencing techniques.

Analyzing the amino acid sequence of SEQ ID NO:281, the putative signalpeptide is at about amino acids 1–19 of SEQ ID NO:281. AnN-glycosylation site is at about amino acids 35–38 of SEQ ID NO:281. AC-type lectin domain is at about amino acids 108–117 of SEQ ID NO:281,indicating that PRO513 may be related to or be a lectin. Thecorresponding nucleotides of these amino acid sequences or others can beroutinely determined given the sequences provided herein.

Example 88 Isolation of cDNA Clones Encoding Human PRO1027

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a certain EST cluster sequence from the Incytedatabase. This EST cluster sequence was then compared to a variety ofexpressed sequence tag (EST) databases which included public ESTdatabases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ®,Incyte Pharmaceuticals, Palo Alto, Calif.) to identify existinghomologies. The homology search was performed using the computer programBLAST or BLAST2 (Altshul et al., Methods in Enzymology 266:460–480(1996)). Those comparisons resulting in a BLAST score of 70 (or in somecases 90) or greater that did not encode known proteins were clusteredand assembled into a consensus DNA sequence with the program “phrap”(Phil Green, University of Washington, Seattle, Wash.). The consensussequence obtained therefrom is herein designated DNA56399.

In light of an observed sequence homology between the DNA56399 sequenceand an EST sequence contained within Incyte EST clone no. 937605, theIncyte EST clone no. 937605 was purchased and the cDNA insert wasobtained and sequenced. It was found that the insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.199 and is herein designated as DNA59605-1418.

The entire nucleotide sequence of DNA59605-1418 is shown in FIG. 199(SEQ ID NO:282). Clone DNA59605-1418 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 31–33 and ending at the stop codon at nucleotide positions262–264 (FIG. 199). The predicted polypeptide precursor is 77 aminoacids long (FIG. 200). The full-length PRO1027 protein shown in FIG. 200has an estimated molecular weight of about 8,772 daltons and a pI ofabout 9.62. Clone DNA59605-1418 has been deposited with the ATCC.Regarding the sequence, it is understood that the deposited clonecontains the correct sequence, and the sequences provided herein arebased on known sequencing techniques.

Analyzing the amino acid sequence of SEQ ID NO:283, the putative signalpeptide is at about amino acids 1–33 of SEQ ID NO:283. The type IIfibronectin collagen-binding domain begins at about amino acid 30 of SEQID NO:283. The corresponding nucleotides for these amino acid sequencesand others can be routinely determined given the sequences providedherein. PRO1027 may be involved in tissue formation or repair.

The following Dayhoff designations appear to have some sequence identitywith PRO1027: SFT2_YEAST; ATM3E9_(—)2; A69826; YM16_MARPO; E64896;U60193_(—)2; MTLRAJ205_(—)1; MCU60315_(—)70; SPAS_SHIFL; and S54213.

Example 89 Isolation of cDNA Clones Encoding Human PRO1107

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a certain EST cluster sequence from the Incytedatabase. This EST cluster sequence was then compared to a variety ofexpressed sequence tag (EST) databases which included public ESTdatabases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ®,Incyte Pharmaceuticals, Palo Alto, Calif.) to identify existinghomologies. The homology search was performed using the computer programBLAST or BLAST2 (Altshul et al., Methods in Enzymology 266:460–480(1996)). Those comparisons resulting in a BLAST score of 70 (or in somecases 90) or greater that did not encode known proteins were clusteredand assembled into a consensus DNA sequence with the program “phrap”(Phil Green, University of Washington, Seattle, Wash.). The consensussequence obtained therefrom is herein designated DNA56402.

In light of an observed sequence homology between the DNA56402 sequenceand an EST sequence contained within Incyte EST clone no. 3203694, theIncyte EST clone no. 3203694 was purchased and the cDNA insert wasobtained and sequenced. It was found that the insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.201 and is herein designated as DNA59606-1471.

The entire nucleotide sequence of DNA59606-1471 is shown in FIG. 201(SEQ ID NO:284). Clone DNA59606-1471 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 244–246 and ending at the stop codon at nucleotide positions1675–1677 of SEQ ID NO:284 (FIG. 201). The predicted polypeptideprecursor is 477 amino acids long (FIG. 202). The full-length PRO1107protein shown in FIG. 202 has an estimated molecular weight of about54,668 daltons and a pI of about 6.33. Clone DNA59606-1471 has beendeposited with ATCC on Jun. 9, 1998. It is understood that the depositedclone has the actual nucleic acid sequence and that the sequencesprovided herein are based on known sequencing techniques.

Analysis of the amino acid sequence of the full-length PRO1107polypeptide suggests that it possesses significant sequence similarityto phosphodiesterase I/nucleotide phyrophosphatase, human insulinreceptor tyrosine kinase inhibitor, alkaline phosphodiesterase andautotaxin, thereby indicating that PRO1107 may have at least one or allof the activities of these proteins, and that PRO1107 is a novelphosphodiesterase. More specifically, an analysis of the Dayhoffdatabase (version 35.45 SwissProt 35) evidenced sequence identitybetween the PRO1107 amino acid sequence and at least the followingDayhoff sequences: AF005632_(—)1, P_R79148, RNU78787_(—)1,AF060218_(—)4, A57080 and HUMATXT_(—)1.

Example 90 Isolation of cDNA Clones Encoding Human PRO1140

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single Incyte EST sequence, Incyte clustersequence No. 135917. This sequence was then compared to a variety ofexpressed sequence tag (EST) databases which included public ESTdatabases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ™M,Incyte Pharmaceuticals, Palo Alto, Calif.) to identify existinghomologies. The homology search was performed using the computer programBLAST or BLAST2 (Altshul et al., Methods in Enzymology 266:460–480(1996)). Those comparisons resulting in a BLAST score of 70 (or in somecases 90) or greater that did not encode known proteins were clusteredand assembled into a consensus DNA sequence with the program “phrap”(Phil Green, Univ. of Washington, Seattle, Wash.). The consensussequence obtained therefrom is herein designated DNA56416.

In light of an observed sequence homology between DNA56416 and an ESTsequence contained within Incyte EST clone no. 3345705, Incyte EST cloneno. 3345705 was obtained and its insert sequenced. It was found that theinsert encoded a full-length protein The sequence, designated herein asDNA59607-1497, which is shown in FIG. 203, is the full-length DNAsequence for PRO1140. Clone DNA59607-1497 was deposited with the ATCC onJun. 9, 1998, and is assigned ATCC deposit no. 209946.

The entire nucleotide sequence of DNA59607-1497 is shown in FIG. 203(SEQ ID NO:286). Clone DNA59607-1497 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 210–212 and ending at the stop codon at nucleotide positions975–977 (FIG. 203). The predicted polypeptide precursor is 255 aminoacids long (FIG. 204). The full-length PRO1140 protein shown in FIG. 204has an estimated molecular weight of about 29,405 daltons and a pI ofabout 7.64. Analysis of the full-length PRO1140 sequence shown in FIG.204 (SEQ ID NO:287) evidences the presence of three transmembranedomains at about amino acids 101 to 118, 141 to 161 and 172 to 191.

Analysis of the amino acid sequence of the full-length PRO1140polypeptide using the Dayhoff database (version 35.45 SwissProt 35)evidenced homology between the PRO1140 amino acid sequence and thefollowing Dayhoff sequences: AF023602_(—)1, AF000368_(—)1, CIN3_RAT,AF003373_(—)1, GEN13279, and AF003372_(—)1.

Clone DNA59607-1497 was deposited with the ATCC on Jun. 9, 1998, and isassigned ATCC deposit no. 209946.

Example 91 Isolation of cDNA Clones Encoding Human PRO1106

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single Incyte EST sequence. This sequencewas then compared to a variety of expressed sequence tag (EST) databaseswhich included public EST databases (e.g., GenBank) and a proprietaryEST DNA database (LIFESEQ™, Incyte Pharmaceuticals, Palo Alto, Calif.)to identify existing homologies. The homology search was performed usingthe computer program BLAST or BLAST2 (Altshul et al., Methods inEnzymology 266:460–480 (1996)). Those comparisons resulting in a BLASTscore of 70 (or in some cases 90) or greater that did not encode knownproteins were clustered and assembled into a consensus DNA sequence withthe program “phrap” (Phil Green, Univ. of Washington, Seattle, Wash.).The consensus sequence obtained therefrom is herein designated DNA56423.

In light of an observed sequence homology between DNA56423 and an ESTsequence contained within Incyte EST clone no. 1711247, Incyte EST cloneno. 1711247 was obtained and its insert sequenced. It was found that theinsert encoded a full-length protein The sequence, designated herein asDNA59609-1470, which is shown in FIG. 205, is the full-length DNAsequence for PRO1106. Clone DNA59609-1470 was deposited with the ATCC onJun. 9, 1998, and is assigned ATCC deposit no. 209963.

The entire nucleotide sequence of DNA59609-1470 is shown in FIG. 205(SEQ ID NO:288). Clone DNA59609-1470 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 61–63 and ending at the stop codon at nucleotide positions1468–1470 of SEQ ID NO:288 (FIG. 205). The predicted polypeptideprecursor is 469 amino acids long (FIG. 206). The full-length PRO1106protein shown in FIG. 206 has an estimated molecular weight of about52,689 daltons and a pI of about 8.68. It is understood that the skilledartisan can construct the polypeptide or nucleic acid encoding thereforto exclude any one or more of all of these domains. For example, thetransmembrane domain region(s) and/or either of the amino terminal orcarboxyl end can be excluded. Clone DNA59609-1470 has been depositedwith ATCC on Jun. 9, 1998. It is understood that the deposited clone hasthe actual nucleic acid sequence and that the sequences provided hereinare based on known sequencing techniques.

Analysis of the amino acid sequence of the full-length PRO1106polypeptide suggests that it possesses significant sequence similarityto the peroxisomal ca-dependent solute carrier, thereby indicating thatPRO1106 may be a novel transporter. More specifically, an analysis ofthe Dayhoff database (version 35.45 SwissProt 35) evidenced sequenceidentity between the PRO1106 amino acid sequence and at least thefollowing Dayhoff sequences, AF004161_(—)1, IG002N01_(—)25, GDC_BOVINand BT1_MAIZE.

Example 92 Isolation of cDNA Clones Encoding Human PRO1291

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of an EST cluster sequence from the Incytedatabase, designated 120480. This EST cluster sequence was then comparedto a variety of expressed sequence tag (EST) databases which includedpublic EST databases (e.g., GenBank) and a proprietary EST DNA database(Lifeseq®, Incyte Pharmaceuticals, Palo Alto, Calif.) to identifyexisting homologies. The homology search was performed using thecomputer program BLAST or BLAST2 (Altshul et al., Methods in Enzymology266:460–480 (1996)). Those comparisons resulting in a BLAST score of 70(or in some cases 90) or greater that did not encode known proteins wereclustered and assembled into a consensus DNA sequence with the program“phrap” (Phil Green, University of Washington, Seattle, Wash.). Theconsensus sequence obtained therefrom is herein designated DNA56425.

In light of an observed sequence homology between the DNA56425 sequenceand an EST sequence encompassed within the Incyte EST clone no. 2798803,the Incyte EST clone 2798803 was purchased and the cDNA insert wasobtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.207 and is herein designated as DNA59610-1556.

Clone DNA59610-1556 contains a single open reading frame with anapparent translational initiation site at nucleotide positions 61–63 andending at the stop codon at nucleotide positions 907–909 (FIG. 207). Thepredicted polypeptide precursor is 282 amino acids long (FIG. 208). Thefull-length PRO1291 protein shown in FIG. 208 has an estimated molecularweight of about 30,878 daltons and a pI of about 5.27. Analysis of thefull-length PRO1291 sequence shown in FIG. 208 (SEQ ID NO:291) evidencesthe presence of the following: a signal peptide from about amino acid 1to about amino acid 28, a transmembrane domain from about amino acid 258to about amino acid 281 and potential N-glycosylation sites from aboutamino acid 112 to about amino acid 115, from about amino acid 160 toabout amino acid 163, from about amino acid 190 to about amino acid 193,from about amino acid 196 to about amino acid 199, from about amino acid205 to about amino acid 208, from about amino acid 216 to about aminoacid 219 and from about amino acid 220 to about amino acid 223. CloneDNA59610-1556 has been deposited with ATCC on Jun. 16, 1998 and isassigned ATCC deposit no. 209990.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 208 (SEQ ID NO:291), evidenced significant homologybetween the PRO1291 amino acid sequence and the following Dayhoffsequences: HSU90552_(—)1, HSU90144_(—)1, AF033107_(—)1, HSB73_(—)1,HSU90142_(—)1, GGCD80_(—)1, P_W34452, MOG_MOUSE, B39371 and P_R71360.

Example 93 Isolation of cDNA Clones Encoding Human PRO1105

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of an EST cluster sequence from the Incytedatabase. This EST cluster sequence was then compared to a variety ofexpressed sequence tag (EST) databases which included public ESTdatabases (e.g., GenBank) and a proprietary EST DNA database (Lifeseq®,Incyte Pharmaceuticals, Palo Alto, Calif.) to identify existinghomologies. The homology search was performed using the computer programBLAST or BLAST2 (Altshul et al., Methods in Enzymology 266:460–480(1996)). Those comparisons resulting in a BLAST score of 70 (or in somecases 90) or greater that did not encode known proteins were clusteredand assembled into a consensus DNA sequence with the program “phrap”(Phil Green, University of Washington, Seattle, Wash.). The consensussequence obtained therefrom is herein designated DNA56430.

In light of an observed sequence homology between the DNA56430 sequenceand an EST sequence encompassed within the Incyte EST clone no. 1853047,the Incyte EST clone 1853047 was purchased and the cDNA insert wasobtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.209 and is herein designated as DNA59612-1466.

The entire nucleotide sequence of DNA59612-1466 is shown in FIG. 209(SEQ ID NO:292). Clone DNA59612-1466 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 28–30 and ending at the stop codon at nucleotide positions568–570 of SEQ ID NO:292 (FIG. 209). The predicted polypeptide precursoris 180 amino acids long (FIG. 210). The full-length PRO1105 proteinshown in FIG. 210 has an estimated molecular weight of about 20,040daltons and a pI of about 8.35. Clone DNA59612-1466 has been depositedwith the ATCC on Jun. 9, 1998. It is understood that the deposited clonehas the actual nucleic acid sequence and that the sequences providedherein are based on known sequencing techniques.

Analyzing FIG. 210, a signal peptide is at about amino acids 1–19 of SEQID NO:293 and transmembrane domains are shown at about amino acids 80–99and 145–162 of SEQ ID NO:293. It is understood that the skilled artisancould form a polypeptide with all of or any combination or individualselection of these regions. It is also understood that the correspondingnucleic acids can be routinely identified and prepared based on theinformation provided herein.

Example 94 Isolation of cDNA Clones Encoding Human PRO511

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of an EST cluster sequence from the Incytedatabase. This EST cluster sequence was then compared to a variety ofexpressed sequence tag (EST) databases which included public ESTdatabases (e.g., GenBank) and a proprietary EST DNA database (Lifeseq®,Incyte Pharmaceuticals, Palo Alto, Calif.) to identify existinghomologies. The homology search was performed using the computer programBLAST or BLAST2 (Altshul et al., Methods in Enzymology 266:460–480(1996)). Those comparisons resulting in a BLAST score of 70 (or in somecases 90) or greater that did not encode known proteins were clusteredand assembled into a consensus DNA sequence with the program “phrap”(Phil Green, University of Washington, Seattle, Wash.). The consensussequence obtained therefrom is herein designated DNA56434.

In light of an observed sequence homology between the DNA56434 sequenceand an EST sequence encompassed within the Incyte EST clone no. 1227491,the Incyte EST clone 1227491 was purchased and the cDNA insert wasobtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.211 and is herein designated as DNA59613-1417.

The entire nucleotide sequence of DNA59613-1417 is shown in FIG. 211(SEQ ID NO:294). Clone DNA59613-1417 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 233–235 and ending at the stop codon at nucleotide positions944–946 (FIG. 211). The predicted polypeptide precursor is 237 aminoacids long (FIG. 212). The full-length PRO511 protein shown in FIG. 212has an estimated molecular weight of about 25,284 daltons and a pI ofabout 5.74. Clone DNA59613-1417 has been deposited with the ATCC.Regarding the sequence, it is understood that the deposited clonecontains the correct sequence, and the sequences provided herein arebased on known sequencing techniques.

Analyzing the amino acid sequence of SEQ ID NO:295, the putative signalpeptide is at about amino acids 1–25 of SEQ ID NO:295. TheN-glycosylation sites are at about amino acids 45–48, 73–76, 107–110,118–121, 132–135, 172–175, 175–178 and 185–188 of SEQ ID NO:295. Anarthropod defensins conserved region is at about amino acids 176–182 ofSEQ ID NO:295. A kringle domain begins at about amino acid 128 of SEQ IDNO:295 and a 1y-6/u-PAR domain begins at about amino acid 6 of SEQ IDNO:295. The corresponding nucleotides of these amino acid sequences andothers can be routinely determined given the sequences provided herein.

The designations appearing in a Dayhoff database with which PRO511 hassome sequence identity are as follows: SSC20F10_(—)1; SF041083;P_W26579; S44208; JC2394; PSTA_DICDI; A27020; S59310;RAG1_RABIT; andMUSBALBC1_(—)1.

Example 95 Isolation of cDNA Clones Encoding Human PRO1104

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of an EST cluster sequence from the Incytedatabase. This EST cluster sequence was then compared to a variety ofexpressed sequence tag (EST) databases which included public ESTdatabases (e.g., GenBank) and a proprietary EST DNA database (Lifeseq®,Incyte Pharmaceuticals, Palo Alto, Calif.) to identify existinghomologies. The homology search was performed using the computer programBLAST or BLAST2 (Altshul et al., Methods in Enzymology 266:460–480(1996)). Those comparisons resulting in a BLAST score of 70 (or in somecases 90) or greater that did not encode known proteins were clusteredand assembled into a consensus DNA sequence with the program “phrap”(Phil Green, University of Washington, Seattle, Wash.). The consensussequence obtained therefrom is herein designated DNA56446.

In light of an observed sequence homology between the DNA56446 sequenceand an EST sequence encompassed within the Incyte EST clone no. 2837496,the Incyte EST clone 2837496 was purchased and the cDNA insert wasobtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.213 and is herein designated as DNA59616-1465.

The entire nucleotide sequence of DNA59616-1465 is shown in FIG. 213(SEQ ID NO:296). Clone DNA59616-1465 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 109–111 and ending at the stop codon at nucleotide positions1132–1134 of SEQ ID NO:296 (FIG. 213). The predicted polypeptideprecursor is 341 amino acids long (FIG. 214). The full-length PRO1104protein shown in FIG. 214 has an estimated molecular weight of about36,769 daltons and a pI of about 9.03. Clone DNA59616-1465 has beendeposited with ATCC on Jun. 16, 1998. It is understood that thedeposited clone has the actual nucleic acid sequence and that thesequences provided herein are based on known sequencing techniques.

Analyzing FIG. 214, a signal peptide is at about amino acids 1–22 of SEQID NO:297. N-myristoylation sites are at about amino acids 41–46,110–115, 133–138, 167–172 and 179–184 of SEQ ID NO:297.

Example 96 Isolation of cDNA Clones Encoding Human PRO1100

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of an EST cluster sequence from the Incytedatabase. This EST cluster sequence was then compared to a variety ofexpressed sequence tag (EST) databases which included public ESTdatabases (e.g., GenBank) and a proprietary EST DNA database (Lifeseq®,Incyte Pharmaceuticals, Palo Alto, Calif.) to identify existinghomologies. The homology search was performed using the computer programBLAST or BLAST2 (Altshul et al., Methods in Enzymology 266:460–480(1996)). Those comparisons resulting in a BLAST score of 70 (or in somecases 90) or greater that did not encode known proteins were clusteredand assembled into a consensus DNA sequence with the program “phrap”(Phil Green, University of Washington, Seattle, Wash.).

In light of an observed sequence homology between the obtained consensussequence and an EST sequence encompassed within the Incyte EST clone no.2305379, the Incyte EST clone 2305379 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.215 and is herein designated as DNA59619-1464.

The entire nucleotide sequence of DNA59619-1464 is shown in FIG. 215(SEQ ID NO:298). Clone DNA59619-1464 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 33–35 and ending at the stop codon at nucleotide positions993–995 of SEQ ID NO:298 (FIG. 215). The predicted polypeptide precursoris 320 amino acids long (FIG. 216). The full-length PRO1100 proteinshown in FIG. 216 has an estimated molecular weight of about 36,475daltons and a pI of about 7.29. Clone DNA59619-1464 has been depositedwith ATCC on Jul. 1, 1998. It is understood that the deposited clone hasthe actual nucleic acid sequence and that the sequences provided hereinare based on known sequencing techniques.

Upon analyzing SEQ ID NO:299, the approximate locations of the signalpeptide, the transmembrane domains, an N-glycosylation site, anN-myristoylation site, a CUB domain and an amiloride-sensitive sodiumchannel domain are present. It is believed that PRO1100 may function asa channel. The corresponding nucleic acids for these amino acids andothers can be routinely determined given SEQ ID NO:299.

Example 97 Isolation of cDNA Clones Encoding Human PRO836

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of an EST cluster sequence from the Incytedatabase. This EST cluster sequence was then compared to a variety ofexpressed sequence tag (EST) databases which included public ESTdatabases (e.g., GenBank) and a proprietary EST DNA database (Lifeseq®,Incyte Pharmaceuticals, Palo Alto, Calif.) to identify existinghomologies. The homology search was performed using the computer programBLAST or BLAST2 (Altshul et al., Methods in Enzymology 266:460–480(1996)). Those comparisons resulting in a BLAST score of 70 (or in somecases 90) or greater that did not encode known proteins were clusteredand assembled into a consensus DNA sequence with the program “phrap”(Phil Green, University of Washington, Seattle, Wash.). The consensussequence obtained is herein designated DNA56453.

In light of an observed sequence homology between the DNA56453 consensussequence and an EST sequence encompassed within the Incyte EST clone no.2610075, the Incyte EST clone 2610075 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.217 and is herein designated as DNA59620-1463.

The entire nucleotide sequence of DNA59620-1463 is shown in FIG. 217(SEQ ID NO:300). Clone DNA59620-1463 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 65–67 and ending at the stop codon at nucleotide positions1448–1450 of SEQ ID NO:300 (FIG. 217). The predicted polypeptideprecursor is 461 amino acids long (FIG. 218). The full-length PRO836protein shown in FIG. 218 has an estimated molecular weight of about52,085 daltons and a pI of about 5.36. Analysis of the full-lengthPRO836 sequence shown in FIG. 218 (SEQ ID NO:301) evidences the presenceof the following: a signal peptide, N-glycosylation sites,N-myristoylation sites, a domain conserved in the YJL126w/YLR351c/yhcXfamily of proteins, and a region having sequence identity with SLS1.Clone DNA59620-1463 has been deposited with ATCC on Jun. 16, 1998. It isunderstood that the deposited clone has the actual nucleic acid sequenceand that the sequences provided herein are based on known sequencingtechniques.

Analysis of the amino acid sequence of the full-length PRO836polypeptide suggests that it possesses some sequence similarity to SLS1,thereby indicating that PRO836 may be involved in protein translocationof the ER. More specifically, an analysis of the Dayhoff database(version 35.45 SwissProt 35) evidenced some homology between the PRO836amino acid sequence and at least the following Dayhoff sequences,S58132, SPBC3B9_(—)1, S66714, CRU40057_(—)1 and IMA_CAEEL.

Example 98 Isolation of cDNA Clones Encoding Human PRO1141

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of an EST cluster sequence from the Incytedatabase, designated 11873. This EST cluster sequence was then comparedto a variety of expressed sequence tag (EST) databases which includedpublic EST databases (e.g., GenBank) and a proprietary EST DNA database(LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, Calif.) to identifyexisting homologies. The homology search was performed using thecomputer program BLAST or BLAST2 (Altshul et al., Methods in Enzymology266:460–480 (1996)). Those comparisons resulting in a BLAST score of 70(or in some cases 90) or greater that did not encode known proteins wereclustered and assembled into a consensus DNA sequence with the program“phrap” (Phil Green, University of Washington, Seattle, Wash.). Theconsensus sequence obtained therefrom is herein designated DNA56518.

In light of an observed sequence homology between the DNA56518 consensussequence and an EST sequence encompassed within the Incyte EST clone no.2679995, the Incyte EST clone 2679995 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.219 and is herein designated as DNA59625-1498.

Clone DNA59625-1498 contains a single open reading frame with anapparent translational initiation site at nucleotide positions 204–206and ending at the stop codon at nucleotide positions 945–947 (FIG. 219).The predicted polypeptide precursor is 247 amino acids long (FIG. 220).The full-length PRO1141 protein shown in FIG. 220 has an estimatedmolecular weight of about 26,840 daltons and a pI of about 8.19.Analysis of the full-length PRO1141 sequence shown in FIG. 220 (SEQ IDNO:303) evidences the presence of the following: a signal peptide fromabout amino acid 1 to about amino acid 19 and transmembrane domains fromabout amino acid 38 to about amino acid 57, from about amino acid 67 toabout amino acid 83, from about amino acid 117 to about amino acid 139and from about amino acid 153 to about amino acid 170. CloneDNA59625-1498 has been deposited with ATCC on Jun. 16, 1998 and isassigned ATCC deposit no. 209992.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 220 (SEQ ID NO:303), evidenced significant homologybetween the PRO1141 amino acid sequence and the following Dayhoffsequences: CEVF36H2L_(—)2, PCRB7PRJ_(—)1, AB000506_(—)1, LEU95008_(—)1,MRU87980_(—)15, YIGM_ECOLI, STU65700_(—)1, GHU62778_(—)1, CYST_SYNY3 andAF009567_(—)1.

Example 99 Isolation of cDNA Clones Encoding Human PRO1132

A consensus DNA sequence was assembled relative to other EST sequencesusing phrap as described in Example 1 above. This consensus sequence isdesignated herein as DNA35934. Based on the DNA35934 consensus sequence,oligonucleotides were synthesized: 1) to identify by PCR a cDNA librarythat contained the sequence of interest, and 2) for use as probes toisolate a clone of the full-length coding sequence for PRO1132.

PCR primers (forward and reverse) were synthesized:

forward PCR primer: 5′-TCCTGTGACCACCCCTCTAACACC-3′ (SEQ ID NO:310) andreverse PCR primer: 5′-CTGGAACATCTGCTGCCCAGATTC-3′ (SEQ ID NO:311).

Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the consensus sequence which had the followingnucleotide sequence:

-   5′-GTCGGATGACAGCAGCAGCCGCATCATCAATGGATCCGACTGCGATATGC-3′ (SEQ ID    NO:312).

In order to screen several libraries for a source of a full-lengthclone, DNA from the libraries was screened by PCR amplification with thePCR primer pair identified above. A positive library was then used toisolate clones encoding the PRO1132 gene using the probe oligonucleotideand one of the PCR primers. RNA for construction of the cDNA librarieswas isolated from human fetal kidney.

DNA sequencing of the clones isolated as described above gave thefull-length DNA sequence for PRO1132 and the derived protein sequencefor PRO1132.

The entire nucleotide sequence of PRO1132 is shown in FIG. 225 (SEQ IDNO:308). Clone DNA59767-1489 contains a single open reading frame withan apparent translational initiation site at nucleotide positions354–356 and a stop codon at nucleotide positions 1233–1235 (FIG. 225;SEQ ID NO:308). The predicted polypeptide precursor is 293 amino acidslong. The signal peptide is at about amino acids 1–22 and the histidineactive site is at about amino acids 104–109 of SEQ ID NO:309. CloneDNA59767-1489 has been deposited with ATCC (having the actual sequencerather than representations based on sequencing techniques as presentedherein) and is assigned ATCC deposit no. 203108. The full-length PRO1132protein shown in FIG. 226 has an estimated molecular weight of about32,020 daltons and a pI of about 8.7.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 226 (SEQ ID NO:309), revealed sequence identity betweenthe PRO1132 amino acid sequence and the following Dayhoff sequences:SSU76256_(—)1, P_W10694, MMAE000663_(—)6, AF013988_(—)1, U66061_(—)8,MMAE000665_(—)2, MMAE00066415, MMAE00066414, MMAE000665_(—)4 andMMAE00066412.

Example 100 Isolation of cDNA Clones Encoding Human NL7 (PRO1346)

A single EST sequence (#1398422) was found in the LIFESEQ® database asdescribed in Example 1 above. This EST sequence was renamed as DNA45668.Based on the DNA45668 sequence, oligonucleotides were synthesized: 1) toidentify by PCR a cDNA library that contained the sequence of interest,and 2) for use as probes to isolate a clone of the full-length codingsequence for NL7.

PCR primers (forward and reverse) were synthesized:

forward PCR primer: 5′-CACACGTCCAACCTCAATGGGCAG-3′ (SEQ ID NO:315)reverse PCR primer: 5′-GACCAGCAGGGCCAAGGACAAGG-3′ (SEQ ID NO:316)

Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the consensus DNA45668 sequence which had the followingnucleotide sequence:

Hybridization Probe

-   5′-GTTCTCTGAGATGAAGATCCGGCCGGTCCGGGAGTACCGCTTAG-3′ (SEQ ID NO:317)

In order to screen several libraries for a source of a full-lengthclone, DNA from the libraries was screened by PCR amplification with thePCR primer pair identified above. A positive library was then used toisolate clones encoding the NL7 gene using the probe oligonucleotide andone of the PCR primers. RNA for construction of the cDNA libraries wasisolated from a human fetal kidney library (LIB227).

DNA sequencing of the clones isolated as described above gave thefull-length DNA sequence for NL7 (designated herein as DNA59776-1600[FIG. 227, SEQ ID NO:313]) and the derived protein sequence for NL7(PRO1346).

The entire coding sequence of NL7 (PRO1346) is shown in FIG. 227 (SEQ IDNO:313). Clone DNA59776-1600 contains a single open reading frame withan apparent translational initiation site at nucleotide positions 1–3and an apparent stop codon at nucleotide positions 1384–1386. Thepredicted polypeptide precursor is 461 amino acids long. The proteincontains an apparent type II transmembrane domain at amino acidpositions from about 31 to about 50; fibrinogen beta and gamma chainsC-terminal domain signature starting at about amino acid position 409,and a leucine zipper pattern starting at about amino acid positions 140,147, 154 and 161, respectively. Clone DNA59776-1600 has been depositedwith ATCC and is assigned ATCC deposit no. 203128. The full-length NL7protein shown in FIG. 228 has an estimated molecular weight of about50,744 daltons and a pI of about 6.38.

Based on a WU-BLAST2 sequence alignment analysis (using the WU-BLAST2computer program) of the full-length sequence, NL7 shows significantamino acid sequence identity to a human microfibril-associatedglycoprotein (1 MFA4_HUMAN); to known TIE-2 ligands and ligandhomologues, ficolin, serum lectin and TGF-1 binding protein.

Example 101 Isolation of cDNA Clones Encoding Human PRO1131

A cDNA sequence isolated in the amylase screen described in Example 2above is herein designated DNA43546 (see FIG. 231; SEQ ID NO:320). TheDNA43546 sequence was then compared to a variety of expressed sequencetag (EST) databases which included public EST databases (e.g., GenBank)and a proprietary EST DNA database (LIFESEQ™, Incyte Pharmaceuticals,Palo Alto, Calif.) to identify existing homologies. The homology searchwas performed using the computer program BLAST or BLAST2 (Altshul etal., Methods in Enzymology 266:460–480 (1996)). Those comparisonsresulting in a BLAST score of 70 (or in some cases 90) or greater thatdid not encode known proteins were clustered and assembled intoconsensus DNA sequences with the program “phrap” (Phil Green, Universityof Washington, Seattle, Wash.). The consensus sequence obtainedtherefrom is herein designated DNA45627.

Based on the DNA45627 sequence, oligonucleotide probes were generatedand used to screen a human library prepared as described in paragraph 1of Example 2 above. The cloning vector was pRK5B (pRK5B is a precursorof pRK5D that does not contain the SfiI site; see, Holmes et al.,Science 253:1278–1280 (1991)), and the cDNA size cut was less than 2800bp.

PCR primers (forward and 2 reverse) were synthesized:

forward PCR primer 5′-ATGCAGGCCAAGTACAGCAGCAC-3′ (SEQ ID NO:321);reverse PCR primer 1 5′-CATGCTGACGACTTCCTGCAAGC-3′ (SEQ ID NO:322); andreverse PCR primer 1 5′-CCACACAGTCTCTGCTTCTTGGG-3′ (SEQ ID NO:323)

Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the DNA45627 sequence which had the followingnucleotide sequence:

Hybridization Probe

-   5′-ATGCTGGATGATGATGGGGACACCCCATGAGCCTGCATT-3′ (SEQ ID NO:324).

In order to screen several libraries for a source of a full-lengthclone, DNA from the libraries was screened by PCR amplification with thePCR primer pair identified above. A positive library was then used toisolate clones encoding the PRO1131 gene using the probe oligonucleotideand one of the PCR primers.

A full length clone was identified that contained a single open readingframe with an apparent translational initiation site at nucleotidepositions 144–146, and a stop signal at nucleotide positions 984–986(FIG. 229; SEQ ID NO:318). The predicted polypeptide precursor is 280amino acids long, has a calculated molecular weight of approximately31,966 daltons and an estimated pI of approximately 6.26. Thetransmembrane domain sequence is at about 49–74 of SEQ ID NO:319 and theregion having sequence identity with LDL receptors is about 50–265 ofSEQ ID NO:319. PRO1131 contains potential N-linked glycosylation sitesat amino acid positions 95–98 and 169–172 of SEQ ID NO:319. CloneDNA59777-1480 has been deposited with the ATCC and is assigned ATCCdeposit no. 203111.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 230 (SEQ ID NO:319), evidenced some sequence identitybetween the PRO1131 amino acid sequence and the following Dayhoffsequences: AB010710_(—)1, I49053, I49115, RNU56863_(—)1, LY4A_MOUSE,I55686, MMU56404_(—)1, I49361, AF030313_(—)1 and MMU09739_(—)1.

Example 102 Isolation of cDNA Clones Encoding Human PRO1281

A consensus DNA sequence was assembled relative to other EST sequencesusing phrap as described in Example 1 above. This consensus sequence isdesignated herein as DNA35720. Based on the DNA35720 sequence,oligonucleotides were synthesized: 1) to identify by PCR a cDNA librarythat contained the sequence of interest, and 2) for use as probes toisolate a clone of the full-length coding sequence for PRO1281.

PCR primers (forward and reverse) were synthesized:

forward PCR primers: 5′-TGGAAGGCTGCCGCAACGA (SEQ ID NO:327); CAATC-3′5′-CTGATGTGGCCGATGTTCTG-3′ (SEQ ID NO:328); and5′-ATGGCTCAGTGTGCAGACAG-3′ (SEQ ID NO:329). reverse PCR primers:5′-GCATGCTGCTCCGTGAAGTA (SEQ ID NO:330); and GTCC-3′5′-ATGCATGGGAAAGAAGGCCT (SEQ ID NO:331). GCCC-3′Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the DNA35720 sequence which had the followingnucleotide sequence:Hybridization Probe

-   5′-TGCACTGGTGACCACGAGGGGGTGCACTATAGCCATCTGGAGCTGAG-3′ (SEQ ID    NO:332).

In order to screen several libraries for a source of a full-lengthclone, DNA from the libraries was screened by PCR amplification with thePCR primer pairs identified above. A positive library was then used toisolate clones encoding the PRO1281 gene using the probe oligonucleotideand one of the PCR primers. RNA for construction of the cDNA librarieswas isolated human fetal liver.

DNA sequencing of the clones isolated as described above gave thefull-length DNA sequence for PRO1281 (designated herein as DNA59820-1549[FIG. 232, SEQ ID NO:325]; and the derived protein sequence for PRO1281.

The entire coding sequence of PRO1281 is shown in FIG. 232 (SEQ IDNO:325). Clone DNA59820-1549 contains a single open reading frame withan apparent translational initiation site at nucleotide positions228–230 and an apparent stop codon at nucleotide positions 2553–2555.The predicted polypeptide precursor is 775 amino acids long. Thefull-length PRO1281 protein shown in FIG. 233 has an estimated molecularweight of about 85,481 daltons and a pI of about 6.92. Additionalfeatures include a signal peptide at about amino acids 1–15; andpotential N-glycosylation sites at about amino acids 138–141 and361–364.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 233 (SEQ ID NO:326), revealed some sequence identitybetween the PRO1281 amino acid sequence and the following Dayhoffsequences: S44860, CET24D1_(—)1, CEC38H2_(—)3, CAC2_HAECO, B3A2_HUMAN,S22373, CEF38A3_(—)2, CEC34F6_(—)2, CEC34F6_(—)3, and CELT22B11_(—)3.

Clone DNA59820-1549 has been deposited with ATCC and is assigned ATCCdeposit no. 203129.

Example 103 Isolation of cDNA Clones Encoding Human PRO1064

A cDNA sequence isolated in the amylase screen described in Example 2above was found, by the WU-BLAST2 sequence alignment computer program,to have no significant sequence identity to any known human protein.This cDNA sequence is herein designated DNA45288. The DNA45288 sequencewas then compared to various EST databases including public ESTdatabases (e.g., GenBank), and a proprietary EST database (LIFESEQ®,Incyte Pharmaceuticals, Palo Alto, Calif.) to identify homologous ESTsequences. The comparison was performed using the computer program BLASTor BLAST2 [Altschul et al., Methods in Enzymology, 266:460–480 (1996)].Those comparisons resulting in a BLAST score of 70 (or in some cases,90) or greater that did not encode known proteins were clustered andassembled into a consensus DNA sequence with the program “phrap” (PhilGreen, University of Washington, Seattle, Wash.). This consensussequence is herein designated DNA48609. Oligonucleotide primers basedupon the DNA48609 sequence were then synthesized and employed to screena human fetal kidney cDNA library which resulted in the identificationof the DNA59827-1426 clone shown in FIG. 234. The cloning vector waspRK5B (pRK5B is a precursor of pRK5D that does not contain the SfiIsite; see, Holmes et al., Science, 253:1278–1280 (1991)), and the cDNAsize cut was less than 2800 bp.

The oligonucleotide probes employed were as follows:

forward PCR primer 5′-CTGAGACCCTGCAGCACCATCTG-3′ (SEQ ID NO:336) reversePCR primer 5′-GGTGCTTCTTGAGCCCCACTTAGC-3′ (SEQ ID NO:337)

Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the consensus DNA48609 sequence which had the followingnucleotide sequence

Hybridization Probe

-   5′-AATCTAGCTTCTCCAGGACTGTGGTCGCCCCGTCCGCTGT-3′ (SEQ ID NO:338)

A full length clone was identified that contained a single open readingframe with an apparent translational initiation site at nucleotidepositions 532–534 and a stop signal at nucleotide positions 991–993(FIG. 234, SEQ ID NO:333). The predicted polypeptide precursor is 153amino acids long, has a calculated molecular weight of approximately17,317 daltons and an estimated pI of approximately 5.17. Analysis ofthe full-length PRO1064 sequence shown in FIG. 235 (SEQ ID NO:334)evidences the presence of the following: a signal peptide from aboutamino acid 1 to about amino acid 24, a transmembrane domain from aboutamino acid 89 to about amino acid 110, an indole-3-glycerol phosphatesynthase homology block from about amino acid 74 to about amino acid 105and a Myb DNA binding domain protein repeat protein homology block fromabout amino acid 114 to about amino acid 137. Clone DNA59827-1426 hasbeen deposited with ATCC on Aug. 4, 1998 and is assigned ATCC depositno. 203089.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 235 (SEQ ID NO:334), evidenced homology between thePRO1064 amino acid sequence and the following Dayhoff sequences:MMNP15PRO_(—)1, BP187PLYH_(—)1, CELF42G8_(—)4, MMU58888_(—)1, GEN14270,TUB8_SOLTU, RCN_MOUSE, HUMRBSY79_(—)1, SESENODA_(—)1 and A21467_(—)1.

Example 104 Isolation of cDNA Clones Encodin2 Human PRO1379

A consensus DNA sequence was assembled relative to other EST sequencesusing phrap as described in Example 1 above. This consensus sequence isdesignated herein DNA45232. Based on the DNA45232 consensus sequence,oligonucleotides were synthesized: 1) to identify by PCR a cDNA librarythat contained the sequence of interest, and 2) for use as probes toisolate a clone of the full-length coding sequence for PRO1379.

PCR primers (forward and reverse) were synthesized:

forward PCR primer 5′-TGGACACCGTACCCTGGTATCTGC-3′ (SEQ ID NO:341)reverse PCR primer 5′-CCAACTCTGAGGAGAGCAAGTGGC-3′ (SEQ ID NO:342)

Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the consensus DNA45232 sequence which had the followingnucleotide sequence:

Hybridization Probe

-   5′-TGTATGTGCACACCCTCACCATCACCTCCAAGGGCAAGGAGAAC-3′ (SEQ ID NO:343).

In order to screen several libraries for a source of a full-lengthclone, DNA from the libraries was screened by PCR amplification with thePCR primer pair identified above. A positive library was then used toisolate clones encoding the PRO1379 gene using the probe oligonucleotideand one of the PCR primers. RNA for construction of the cDNA librarieswas isolated human fetal kidney tissue.

DNA sequencing of the clones isolated as described above gave thefull-length DNA sequence for PRO1379 which is designated herein asDNA59828-1608 and shown in FIG. 237 (SEQ ID NO:339); and the derivedprotein sequence for PRO1379 (SEQ ID NO:340).

The entire coding sequence of PRO1379 is shown in FIG. 237 (SEQ IDNO:339). Clone DNA59828-1608 contains a single open reading frame withan apparent translational initiation site at nucleotide positions 10–12and an apparent stop codon at nucleotide positions 1732–1734. Thepredicted polypeptide precursor is 574 amino acids long. The full-lengthPRO1379 protein shown in FIG. 238 has an estimated molecular weight ofabout 65,355 daltons and a pI of about 8.73. Additional features includea signal peptide at about amino acids 1–17 and potential N-glycosylationsites at about amino acids 160–163, 287–290, and 323–326.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 238 (SEQ ID NO:340), revealed some homology between thePRO1379 amino acid sequence and the following Dayhoff sequences:YHY8_YEAST, AF040625_(—)1, HP714394_(—)1, and HIV18U45630_(—)1.

Clone DNA59828-1608 has been deposited with ATCC and is assigned ATCCdeposit no. 203158.

Example 105 Isolation of cDNA Clones Encoding Human PRO844

An expressed sequence tag (EST) DNA database (LIFESEQ™, IncytePharmaceuticals, Palo Alto, Calif.) was searched and an EST wasidentified which showed sequence identity with aLP. Based on theinformation and discoveries provided herein, the clone for this EST,Incyte clone no. 2657496 from a cancerous lung library was furtherexamined.

DNA sequencing of the insert for this clone gave a sequence (hereindesignated as DNA59838-1462; SEQ ID NO:344) which includes thefull-length DNA sequence for PRO844 and the derived protein sequence forPRO844.

The entire nucleotide sequence of DNA59838-1462 is shown in FIG. 239(SEQ ID NO:344). Clone DNA59838-1462 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 5–7 and ending at the stop codon at nucleotide positions338–340 of SEQ ID NO:344 (FIG. 239). The predicted polypeptide precursoris 111 amino acids long (FIG. 240). The full-length PRO844 protein shownin FIG. 240 has an estimated molecular weight of about 12,050 daltonsand a pI of about 5.45. Clone UNQ544 DNA59838-1462 has been depositedwith ATCC on Jun. 16, 1998. It is understood that the deposited clonehas the actual nucleic acid sequence and that the sequences providedherein are based on known sequencing techniques.

Analysis of the amino acid sequence of the full-length PRO844polypeptide suggests that it possesses significant sequence similarityto serine protease inhibitors, thereby indicating that PRO844 may be anovel proteinase inhibitor. More specifically, an analysis of theDayhoff database (version 35.45 SwissProt 35) evidenced significanthomology between the PRO844 amino acid sequence and at least thefollowing Dayhoff sequences, ALK1_HUMAN, P_P82403, P_P82402, ELAF_HUMANand P_P60950.

Example 106 Isolation of cDNA Clones Encoding Human PRO848

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single EST cluster sequence from the Incytedatabase. This EST cluster sequence was then compared to a variety ofexpressed sequence tag (EST) databases which included public ESTdatabases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ®,Incyte Pharmaceuticals, Palo Alto, Calif.) to identify existinghomologies. The homology search was performed using the computer programBLAST or BLAST2 (Altshul et al., Methods in Enzymology 266:460–480(1996)). Those comparisons resulting in a BLAST score of 70 (or in somecases 90) or greater that did not encode known proteins were clusteredand assembled into a consensus DNA sequence with the program “phrap”(Phil Green, University of Washington, Seattle, Wash.). The consensussequence obtained therefrom is herein designated DNA55999.

In light of an observed sequence homology between the DNA55999 consensussequence and an EST sequence encompassed within the Incyte EST cloneno.2768571, the Incyte EST clone 2768571 was purchased and the cDNAinsert was obtained and sequenced. It was found that this insert encodeda full-length protein. The sequence of this cDNA insert is shown in FIG.241 and is herein designated as DNA59839-1461.

The entire nucleotide sequence of DNA59839-1461 is shown in FIG. 241(SEQ ID NO:346). Clone DNA59839-1461 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 146–148 and ending at the stop codon at nucleotide positions1946–1948 of SEQ ID NO:346 (FIG. 241). The predicted polypeptideprecursor is 600 amino acids long (FIG. 242). The full-length PRO848protein shown in FIG. 242 has an estimated molecular weight of about68,536 daltons. Clone DNA59839-1461 has been deposited with ATCC on Jun.16, 1998. It is understood that the deposited clone has the actualnucleic acid sequence and that the sequences provided herein are basedon known sequencing techniques.

Analysis of the amino acid sequence of the full-length PRO848polypeptide suggests that it may be a novel sialyltransferase. Morespecifically, an analysis of the Dayhoff database (version 35.45SwissProt 35) evidenced sequence identity between the PRO848 amino acidsequence and at least the following Dayhoff sequences, P_R78619(GalNAc-alpha-2,6-sialyltransferase), CAAG5_CHICK(alpha-n-acetylgalactosamide alpha-2, 6-sialytransferase),HSU14550_(—)1, CAG6_HUMAN and P_R63217 (human alpha-2,3-sialyltransferase).

Example 107 Isolation of cDNA Clones Encoding Human PRO1097

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single EST cluster sequence from the Incytedatabase. This EST cluster sequence was then compared to a variety ofexpressed sequence tag (EST) databases which included public ESTdatabases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ®,Incyte Pharmaceuticals, Palo Alto, Calif.) to identify existinghomologies. The homology search was performed using the computer programBLAST or BLAST2 (Altshul et al., Methods in Enzymology 266:460–480(1996)). Those comparisons resulting in a BLAST score of 70 (or in somecases 90) or greater that did not encode known proteins were clusteredand assembled into a consensus DNA sequence with the program “phrap”(Phil Green, University of Washington, Seattle, Wash.). The consensussequence obtained therefrom is herein designated DNA56006.

In light of an observed sequence homology between the DNA56006 consensussequence and an EST sequence encompassed within the Incyte EST clone no.2408105, the Incyte EST clone 2408105 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.243 and is herein designated as DNA59841-1460.

The entire nucleotide sequence of DNA59841-1460 is shown in FIG. 243(SEQ ID NO:348). Clone DNA59841-1460 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 3–5 and ending at the stop codon at nucleotide positions276–278 of SEQ ID NO:348 (FIG. 243). The predicted polypeptide precursoris 91 amino acids long (FIG. 244). The full-length PRO1097 protein shownin FIG. 244 has an estimated molecular weight of about 10,542 daltonsand a pI of about 10.04. Clone DNA59841-1460 has been deposited withATCC on Jul. 1, 1998. It is understood that the deposited clone has theactual nucleic acid sequence and that the sequences provided herein arebased on known sequencing techniques.

Analyzing FIG. 244, the signal peptide is at about amino acids 1–20 ofSEQ ID NO:349. The glycoprotease family protein domain starts at aboutamino acid 56, and the acyltransferase ChoActase/COT/CPT family peptidestarts at about amino acid 49 of SEQ ID NO:349.

Example 108 Isolation of cDNA Clones Encoding Human PRO1153

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single EST cluster sequence from the Incytedatabase. This EST cluster sequence was then compared to a variety ofexpressed sequence tag (EST) databases which included public ESTdatabases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ®,Incyte Pharmaceuticals, Palo Alto, Calif.) to identify existinghomologies. The homology search was performed using the computer programBLAST or BLAST2 (Altshul et al., Methods in Enzymology 266:460–480(1996)). Those comparisons resulting in a BLAST score of 70 (or in somecases 90) or greater that did not encode known proteins were clusteredand assembled into a consensus DNA sequence with the program “phrap”(Phil Green, University of Washington, Seattle, Wash.). The consensussequence obtained therefrom is herein designated DNA56008.

In light of an observed sequence homology between the DNA56008 consensussequence and an EST sequence encompassed within the Incyte EST clone no.2472409, the Incyte EST clone 2472409 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.245 and is herein designated as DNA59842-1502.

The full length clone shown in FIG. 245 contained a single open readingframe with an apparent translational initiation site at nucleotidepositions 92–94 and ending at the stop codon found at nucleotidepositions 683–685 (FIG. 245; SEQ ID NO:350). The predicted polypeptideprecursor (FIG. 246, SEQ ID NO:351) is 197 amino acids long. PRO1153 hasa calculated molecular weight of approximately 21,540 daltons and anestimated pI of approximately 8.31. Clone DNA59842-1502 has beendeposited with ATCC and is assigned ATCC deposit no. 209982. It isunderstood that the correct and actual sequence is in the depositedclone while herein are present representations based on currentsequencing techniques which may have minor errors.

Based on a WU-BLAST2 sequence alignment analysis (using the ALIGNcomputer program) of the full-length sequence, PRO1153 shows some aminoacid sequence identity to the following Dayhoff designations: S57447;SOYHRGPC_(—)1; S46965; P_P82971; VCPHEROPH_(—)1; EXTN_TOBAC;MLCB2548_(—)9; ANXA_RABIT; JC5437 and SSGP_VOLCA.

Example 109 Isolation of cDNA Clones Encoding Human PRO1154

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single EST cluster sequence from the Incytedatabase. This EST cluster sequence was then compared to a variety ofexpressed sequence tag (EST) databases which included public ESTdatabases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ@,Incyte Pharmaceuticals, Palo Alto, Calif.) to identify existinghomologies. The homology search was performed using the computer programBLAST or BLAST2 (Altshul et al., Methods in Enzymology 266:460–480(1996)). Those comparisons resulting in a BLAST score of 70 (or in somecases 90) or greater that did not encode known proteins were clusteredand assembled into a consensus DNA sequence with the program “phrap”(Phil Green, University of Washington, Seattle, Wash.). The consensussequence obtained therefrom is herein designated DNA56025.

In light of an observed sequence homology between the DNA56025 consensussequence and an EST sequence encompassed within the Incyte EST clone no.2169375, the Incyte EST clone 2169375 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.247 and is herein designated as DNA59846-1503.

The full length clone shown in FIG. 247 contained a single open readingframe with an apparent translational initiation site at nucleotidepositions 86–88 and ending at the stop codon found at nucleotidepositions 2909–2911 (FIG. 247; SEQ ID NO:352). The predicted polypeptideprecursor (FIG. 248, SEQ ID NO:353) is 941 amino acids long. PRO1154 hasa calculated molecular weight of approximately 107,144 daltons and anestimated pI of approximately 6.26. Clone DNA59846-1503 has beendeposited with ATCC and is assigned ATCC deposit no. 209978.

Based on a WU-BLAST2 sequence alignment analysis (using the ALIGNcomputer program) of the full-length sequence, PRO1154 shows sequenceidentity to at least the following Dayhoff designations: AB011097_(—)1,AMPN_HUMAN, RNU76997_(—)1, 159331, GEN14047, HSU62768_(—)1, P_R51281,CET07F10_(—)1, SSU66371_(—)1, and AMPRE_HUMAN.

Example 110 Isolation of cDNA Clones Encoding Human PRO1181

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single EST cluster sequence from the Incytedatabase, designated herein as 82468. This EST cluster sequence was thencompared to a variety of expressed sequence tag (EST) databases whichincluded public EST databases (e.g., GenBank) and a proprietary EST DNAdatabase (LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, Calif.) toidentify existing homologies. The homology search was performed usingthe computer program BLAST or BLAST2 (Altshul et al., Methods inEnzymology 266:460–480 (1996)). Those comparisons resulting in a BLASTscore of 70 (or in some cases 90) or greater that did not encode knownproteins were clustered and assembled into a consensus DNA sequence withthe program “phrap” (Phil Green, University of Washington, Seattle,Wash.). The consensus sequence obtained therefrom is herein designatedDNA56029.

In light of an observed sequence homology between the DNA56029 consensussequence and an EST sequence encompassed within the Incyte EST clone no.2186536, the Incyte EST clone 2186536 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.249 and is herein designated as DNA59847-1511.

Clone DNA59847-1511 contains a single open reading frame with anapparent translational initiation site at nucleotide positions 17–19 andending at the stop codon at nucleotide positions 1328–1330 (FIG. 249).The predicted polypeptide precursor is 437 amino acids long (FIG. 250).The full-length PRO1181 protein shown in FIG. 250 has an estimatedmolecular weight of about 46,363 daltons and a pI of about 6.22.Analysis of the full-length PRO1181 sequence shown in FIG. 250 (SEQ IDNO:355) evidences the presence of the following: a signal peptide fromabout amino acid 1 to about amino acid 15, potential N-glycosylationsites from about amino acid 46 to about amino acid 49, from about aminoacid 189 to about amino acid 192 and from about amino acid 382 to aboutamino acid 385 and amino acid sequence blocks having homology toLy-6/u-PAR domain proteins from about amino acid 287 to about amino acid300 and from about amino acid 98 to about amino acid 111. CloneDNA59847-1511 has been deposited with ATCC on Aug. 4, 1998 and isassigned ATCC deposit no. 203098.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 250 (SEQ ID NO:355), evidenced homology between thePRO1181 amino acid sequence and the following Dayhoff sequences:AF041083_(—)1, P_W26579, RNMAGPIAN_(—)1, CELT13C2_(—)2, LMSAP2GN_(—)1,S61882, CEF35C5_(—)12, DP87_DICDI, GIU47631_(—)1 and P_R07092.

Example 111 Isolation of cDNA Clones Encoding Human PRO1182

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single EST cluster sequence from the Incytedatabase, designated herein as 146647. This EST cluster sequence wasthen compared to a variety of expressed sequence tag (EST) databaseswhich included public EST databases (e.g., GenBank) and a proprietaryEST DNA database (LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, Calif.)to identify existing homologies. The homology search was performed usingthe computer program BLAST or BLAST2 (Altshul et al., Methods inEnzymology 266:460–480 (1996)). Those comparisons resulting in a BLASTscore of 70 (or in some cases 90) or greater that did not encode knownproteins were clustered and assembled into a consensus DNA sequence withthe program “phrap” (Phil Green, University of Washington, Seattle,Wash.). The consensus sequence obtained therefrom is herein designatedDNA56033.

In light of an observed sequence homology between the DNA56033 consensussequence and an EST sequence encompassed within the Incyte EST clone no.2595195, the Incyte EST clone 2595195 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.251 and is herein designated as DNA59848-1512.

Clone DNA59848-1512 contains a single open reading frame with anapparent translational initiation site at nucleotide positions 67–69 andending at the stop codon at nucleotide positions 880–882 (FIG. 251). Thepredicted polypeptide precursor is 271 amino acids long (FIG. 252). Thefull-length PRO1182 protein shown in FIG. 252 has an estimated molecularweight of about 28,665 daltons and a pI of about 5.33. Analysis of thefull-length PRO1182 sequence shown in FIG. 252 (SEQ ID NO:357) evidencesthe presence of the following: a signal peptide from about amino acid 1to about amino acid 25, an amino acid block having homology to C-typelectin domain proteins from about amino acid 247 to about amino acid 256and an amino acid sequence block having homology to C1q domain proteinsfrom about amino acid 44 to about amino acid 77. Clone DNA59848-1512 hasbeen deposited with ATCC on Aug. 4, 1998 and is assigned ATCC depositno. 203088.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 252 (SEQ ID NO:357), evidenced significant homologybetween the PRO1182 amino acid sequence and the following Dayhoffsequences: PSPD_BOVIN, CL43_BOVIN, CONG_BOVIN, P_W18780, P_R45005,P_R53257 and CELEGAP7_(—)1.

Example 112 Isolation of cDNA Clones Encoding Human PRO1155

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single EST cluster sequence from the Incytedatabase. This EST cluster sequence was then compared to a variety ofexpressed sequence tag (EST) databases which included public ESTdatabases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ®,Incyte Pharmaceuticals, Palo Alto, Calif.) to identify existinghomologies. The homology search was performed using the computer programBLAST or BLAST2 (Altshul et al., Methods in Enzymology 266:460–480(1996)). Those comparisons resulting in a BLAST score of 70 (or in somecases 90) or greater that did not encode known proteins were clusteredand assembled into a consensus DNA sequence with the program “phrap”(Phil Green, University of Washington, Seattle, Wash.). The consensussequence obtained therefrom is herein designated DNA56102.

In light of an observed sequence homology between the DNA56102 consensussequence and an EST sequence encompassed within the Incyte EST clone no.2858870, the Incyte EST clone 2858870 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.253 and is herein designated as DNA59849-1504.

The full length clone shown in FIG. 253 contained a single open readingframe with an apparent translational initiation site at nucleotidepositions 158–160 and ending at the stop codon found at nucleotidepositions 563–565 (FIG. 253; SEQ ID NO:358). The predicted polypeptideprecursor (FIG. 254, SEQ ID NO:359) is 135 amino acids long. PRO1155 hasa calculated molecular weight of approximately 14,833 daltons and anestimated pI of approximately 9.78. Clone DNA59849-1504 has beendeposited with ATCC and is assigned ATCC deposit no. 209986. It isunderstood that the actual clone has the correct sequence whereas hereinare only representations which are prone to minor sequencing errors.

Based on a WU-BLAST2 sequence alignment analysis (using the ALIGNcomputer program) of the full-length sequence, PRO1155 shows some aminoacid sequence identity with the following Dayhoff designations:TKNK_BOVIN; PVB19X587_(—)1; AF019049_(—)1; P_W00948; S72864; P_W00949;I62742; AF038501_(—)1; TKNG_HUMAN; and YAT1_RHOBL. Based on theinformation provided herein, PRO1155 may play a role in providingneuroprotection and cognitive enhancement.

Example 113 Isolation of cDNA Clones Encoding Human PRO1156

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single EST cluster sequence from the Incytedatabase, designated herein as 138851. This EST cluster sequence wasthen compared to a variety of expressed sequence tag (EST) databaseswhich included public EST databases (e.g., GenBank) and a proprietaryEST DNA database (LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, Calif.)to identify existing homologies. The homology search was performed usingthe computer program BLAST or BLAST2 (Altshul et al., Methods inEnzymology 266:460–480 (1996)). Those comparisons resulting in a BLASTscore of 70 (or in some cases 90) or greater that did not encode knownproteins were clustered and assembled into a consensus DNA sequence withthe program “phrap” (Phil Green, University of Washington, Seattle,Wash.). The consensus sequence obtained therefrom is herein designatedDNA56261.

In light of an observed sequence homology between the DNA56261 consensussequence and an EST sequence encompassed within the Incyte EST clone no.3675191, the Incyte EST clone 3675191 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.255 and is herein designated as DNA59853-1505.

The full length clone shown in FIG. 255 contained a single open readingframe with an apparent translational initiation site at nucleotidepositions 212–214 and ending at the stop codon found at nucleotidepositions 689–691 (FIG. 255; SEQ ID NO:360). The predicted polypeptideprecursor (FIG. 256, SEQ ID NO:361) is 159 amino acids long. PRO1156 hasa calculated molecular weight of approximately 17,476 daltons, anestimated pI of approximately 9.15, a signal peptide sequence at aboutamino acids 1 to about 22, and potential N-glycosylation sites at aboutamino acids 27–30 and 41–44.

Clone DNA59853-1505 was deposited with the ATCC on Jun. 16, 1998 and isassigned ATCC deposit no. 209985.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis (using the ALIGN computerprogram) of the full-length sequence shown in FIG. 256 (SEQ ID NO:361),revealed some homology between the PRO1156 amino acid sequence and thefollowing Dayhoff sequences: D45027_(—)1, P_R79914, JC5309, KBF2_HUMAN,AF010144_(—)1, GEN14351, S68681, P_R79915, ZMTAC_(—)3, and HUMCPGO_(—)1.

Example 114 Isolation of cDNA Clones Encoding Human PRO1098

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single EST cluster sequence from the Incytedatabase. This EST cluster sequence was then compared to a variety ofexpressed sequence tag (EST) databases which included public ESTdatabases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ®,Incyte Pharmaceuticals, Palo Alto, Calif.) to identify existinghomologies. The homology search was performed using the computer programBLAST or BLAST2 (Altshul et al., Methods in Enzymology 266:460–480(1996)). Those comparisons resulting in a BLAST score of 70 (or in somecases 90) or greater that did not encode known proteins were clusteredand assembled into a consensus DNA sequence with the program “phrap”(Phil Green, University of Washington, Seattle, Wash.). The consensussequence obtained therefrom is herein designated DNA56377.

In light of an observed sequence homology between the DNA56377 consensussequence and an EST sequence encompassed within the Incyte EST clone no.3050917, the Incyte EST clone 3050917 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.257 and is herein designated as DNA59854-1459.

The entire nucleotide sequence of DNA59854-1459 is shown in FIG. 257(SEQ ID NO:362). Clone DNA59854-1459 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 58–60 and ending at the stop codon at nucleotide positions292–294 of SEQ ID NO:362 (FIG. 257). The predicted polypeptide precursoris 78 amino acids long (FIG. 258). The full-length PRO1098 protein shownin FIG. 258 has an estimated molecular weight of about 8,396 daltons anda pI of about 7.66. Clone DNA59854-1459 has been deposited with ATCC onJun. 16, 1998. It is understood that the deposited clone has the actualnucleic acid sequence and that the sequences provided herein are basedon known sequencing techniques.

Analyzing FIG. 258, a signal peptide appears to be at about amino acids1–19 of SEQ ID NO:363, an N-glycosylation site appears to be at aboutamino acids 37–40 of SEQ ID NO:363, and N-myristoylation sites appear tobe at about 15–20, 19–24 and 60–65 of SEQ ID NO:363.

Example 115 Isolation of cDNA Clones Encoding Human PRO1127

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single EST cluster sequence from the Incytedatabase. This EST cluster sequence was then compared to a variety ofexpressed sequence tag (EST) databases which included public ESTdatabases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ®,Incyte Pharmaceuticals, Palo Alto, Calif.) to identify existinghomologies. The homology search was performed using the computer programBLAST or BLAST2 (Altshul et al., Methods in Enzymology 266:460–480(1996)). Those comparisons resulting in a BLAST score of 70 (or in somecases 90) or greater that did not encode known proteins were clusteredand assembled into a consensus DNA sequence with the program “phrap”(Phil Green, University of Washington, Seattle, Wash.). The consensussequence obtained therefrom is herein designated DNA57959.

In light of an observed sequence homology between the DNA57959 consensussequence and an EST sequence encompassed within the Merck EST clone no.685126, the Merck EST clone 685126 was purchased and the cDNA insert wasobtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.259 and is herein designated as DNA60283-1484.

The full length clone shown in FIG. 259 contained a single open readingframe with an apparent translational initiation site at nucleotidepositions 126–128 and ending at the stop codon found at nucleotidepositions 327–329 (FIG. 259; SEQ ID NO:364). The predicted polypeptideprecursor (FIG. 260, SEQ ID NO:365) is 67 amino acids long including asignal peptide at about 1–29 of SEQ ID NO:365. PRO1127 has a calculatedmolecular weight of approximately 7,528 daltons and an estimated pI ofapproximately 4.95. Clone DNA60283-1484 was deposited with the ATCC onJul. 1, 1998 and is assigned ATCC deposit no. 203043. It is understoodthat the deposited clone has the actual sequence, whereasrepresentations which may have minor sequencing errors are presentedherein.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 260 (SEQ ID NO:365), revealed some homology between thePRO1127 amino acid sequence and the following Dayhoff sequences:AF037218_(—)48, P_W09638, HBA_HETPO, S39821, KR2_EBV, CET20D3_(—)8,HCU37630_(—)1, HS193B12_(—)10, S40012 and TRITUBC_(—)1.

Example 116 Isolation of cDNA Clones Encoding Human PRO1126

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single EST cluster sequence from the Incytedatabase. This EST cluster sequence was then compared to a variety ofexpressed sequence tag (EST) databases which included public ESTdatabases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ®,Incyte Pharmaceuticals, Palo Alto, Calif.) to identify existinghomologies. The homology search was performed using the computer programBLAST or BLAST2 (Altshul et al., Methods in Enzymology 266:460–480(1996)). Those comparisons resulting in a BLAST score of 70 (or in somecases 90) or greater that did not encode known proteins were clusteredand assembled into a consensus DNA sequence with the program “phrap”(Phil Green, University of Washington, Seattle, Wash.). The consensussequence obtained therefrom is herein designated DNA56250.

In light of an observed sequence homology between the DNA56250 consensussequence and an EST sequence encompassed within the Incyte EST clone no.1437250, the Incyte EST clone 1437250 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.261 and is herein designated as DNA60615-1483.

Clone DNA60615-1483 contains a single open reading frame with anapparent translational initiation site at nucleotide positions 110–112and ending at the stop codon at nucleotide positions 1316–1318 (FIG.261). The predicted polypeptide precursor is 402 amino acids long (FIG.262). The full-length PRO1126 protein shown in FIG. 262 has an estimatedmolecular weight of about 45,921 daltons and a pI of about 8.60.Analysis of the full-length PRO1126 sequence shown in FIG. 262 (SEQ IDNO:367) evidences the presence of the following: a signal peptide fromabout amino acid 1 to about amino acid 25 and potential N-glycosylationsites from about amino acid 66 to about amino acid 69, from about aminoacid 138 to about amino acid 141 and from about amino acid 183 to aboutamino acid 186. Clone DNA60615-1483 has been deposited with ATCC on Jun.16, 1998 and is assigned ATCC deposit no. 209980.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 262 (SEQ ID NO:367), evidenced significant homologybetween the PRO1126 amino acid sequence and the following Dayhoffsequences: I73636, NOMR_HUMAN, MMUSMYOC3_(—)1, HS454G6_(—)1, P_R98225,RNU78105_(—)1, RNU72487_(—)1, AF035301_(—)1, CEELC48E7_(—)4 andCEF11C3_(—)3.

Example 117 Isolation of cDNA Clones Encoding Human PRO1125

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single EST cluster sequence from the Incytedatabase. This EST cluster sequence was then compared to a variety ofexpressed sequence tag (EST) databases which included public ESTdatabases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ®,Incyte Pharmaceuticals, Palo Alto, Calif.) to identify existinghomologies. The homology search was performed using the computer programBLAST or BLAST2 (Altshul et al., Methods in Enzymology 266:460–480(1996)). Those comparisons resulting in a BLAST score of 70 (or in somecases 90) or greater that did not encode known proteins were clusteredand assembled into a consensus DNA sequence with the program “phrap”(Phil Green, University of Washington, Seattle, Wash.). The consensussequence obtained therefrom is herein designated DNA56540.

In light of an observed sequence homology between the DNA56540 consensussequence and an EST sequence encompassed within the Incyte EST clone no.1486114, the Incyte EST clone 1486114 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.263 and is herein designated as DNA60615-1483.

The full length clone shown in FIG. 263 contained a single open readingframe with an apparent translational initiation site at nucleotidepositions 47–49 and ending at the stop codon found at nucleotidepositions 1388–1390 (FIG. 263; SEQ ID NO:368). The predicted polypeptideprecursor (FIG. 264, SEQ ID NO:369) is 447 amino acids long. PRO125 hasa calculated molecular weight of approximately 49,798 daltons and anestimated pI of approximately 9.78. Clone DNA60619-1482 has beendeposited with ATCC and is assigned ATCC deposit no. 209993. It isunderstood that the clone has the actual sequence and that the sequencesherein are representations based on current techniques which may beprone to minor errors.

Based on a WU-BLAST2 sequence alignment analysis (using the ALIGNcomputer program) of the full-length sequence, PRO1125 shows somesequence identity with the following Dayhoff designations: RCO1_NEUCR;S58306; PKWA_THECU; S76086; P_R85881; HET1_PODAN; SPU92792_(—)1;APAF_HUMAN; S76414 and S59317.

Example 118 Isolation of cDNA Clones Encoding Human PRO1186

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single EST cluster sequence from the Incytedatabase. This EST cluster sequence was then compared to a variety ofexpressed sequence tag (EST) databases which included public ESTdatabases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ®,Incyte Pharmaceuticals, Palo Alto, Calif.) to identify existinghomologies. The homology search was performed using the computer programBLAST or BLAST2 (Altshul et al., Methods in Enzymology 266:460–480(1996)). Those comparisons resulting in a BLAST score of 70 (or in somecases 90) or greater that did not encode known proteins were clusteredand assembled into a consensus DNA sequence with the program “phrap”(Phil Green, University of Washington, Seattle, Wash.). The consensussequence obtained therefrom is herein designated DNA56748.

In light of an observed sequence homology between the DNA56748 consensussequence and an EST sequence encompassed within the Incyte EST clone no.3476792, the Incyte EST clone 3476792 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.265 and is herein designated as DNA60621-1516.

The full length clone shown in FIG. 265 contained a single open readingframe with an apparent translational initiation site at nucleotidepositions 91–93 and ending at the stop codon found at nucleotidepositions 406–408 (FIG. 265; SEQ ID NO:370). The predicted polypeptideprecursor (FIG. 266, SEQ ID NO:371) is 105 amino acids long. The signalpeptide is at amino acids 1–19 of SEQ ID NO:371. PRO1186 has acalculated molecular weight of approximately 11,715 daltons and anestimated pI of approximately 9.05. Clone DNA60621-1516 was depositedwith the ATCC on Aug. 4, 1998 and is assigned ATCC deposit no. 203091.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 266 (SEQ ID NO:371), revealed some sequence identitybetween the PRO1186 amino acid sequence and the following Dayhoffsequences: VPRA_DENPO, LFE4_CHICK, AF034208_(—)1, AF030433_(—)1, A55035,COL_RABIT, CELB0507_(—)9, S67826_(—)1, S34665 and CRU73817_(—)1.

Example 119 Isolation of cDNA Clones Encoding Human PRO1198

An initial DNA sequence referred to herein as DNA52083 was identifiedusing a yeast screen in a human umbilical vein endothelial cell cDNAlibrary that preferentially represents the 5′ ends of the primary cDNAclones. DNA52083 was compared to ESTs from public databases (e.g.,GenBank), and a proprietary EST database (LIFESEQ®, IncytePharmaceuticals, Palo Alto, Calif.), using the computer program BLAST orBLAST2 [Altschul et al., Methods in Enzymology, 266:460–480 (1996)]. TheESTs were clustered and assembled into a consensus DNA sequence usingthe computer program “phrap” (Phil Green, University of Washington,Seattle, Wash.). One or more of the ESTs was obtained from human breastskin tissue biopsy. This consensus sequence is designated herein asDNA52780.

In light of an observed sequence homology between the DNA52780 consensussequence and an EST sequence encompassed within the Incyte EST clone no.3852910, the Incyte EST clone 3852910 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.267 and is herein designated as DNA60622-1525.

The full length DNA60622-1525 clone shown in FIG. 267 (SEQ ID NO:372)contained a single open reading frame with an apparent translationalinitiation site at nucleotide positions 54 to 56 and ending at the stopcodon found at nucleotide positions 741 to 743. The predictedpolypeptide precursor, which is shown in FIG. 268 (SEQ ID NO:373), is229 amino acids long. PRO1198 has a calculated molecular weight ofapproximately 25,764 daltons and an estimated pI of approximately 9.17.There is a signal peptide sequence at about amino acids 1 through 34.There is sequence identity with glycosyl hydrolases family 31 protein atabout amino acids 142 to about 175.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 268 (SEQ ID NO:373), revealed some homology between thePRO1198 amino acid sequence and the following Dayhoff sequences:ATF6H11_(—)6, UCRI_RAT, TOBSUP2NT_(—)1, RCUERF3_(—)1, AMU88186_(—)1,P_W22485, S56579, AF040711_(—)1, DPP4_PIG.

Clone DNA60622-1525 was been deposited with the ATCC on Aug. 4, 1998,and is assigned ATCC deposit no. 203090.

Example 120 Isolation of cDNA Clones Encoding Human PRO1158

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single EST cluster sequence from the Incytedatabase. This EST cluster sequence was then compared to a variety ofexpressed sequence tag (EST) databases which included public ESTdatabases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ®,Incyte Pharmaceuticals, Palo Alto, Calif.) to identify existinghomologies. The homology search was performed using the computer programBLAST or BLAST2 (Altshul et al., Methods in Enzymology 266:460–480(1996)). Those comparisons resulting in a BLAST score of 70 (or in somecases 90) or greater that did not encode known proteins were clusteredand assembled into a consensus DNA sequence with the program “phrap”(Phil Green, University of Washington, Seattle, Wash.). The consensussequence obtained therefrom is herein designated DNA57248.

In light of an observed sequence homology between the DNA57248 consensussequence and an EST sequence encompassed within the Incyte EST clone no.2640776, the Incyte EST clone 2640776 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.269 and is herein designated as DNA60625-1507.

The full length clone shown in FIG. 269 contained a single open readingframe with an apparent translational initiation site at nucleotidepositions 163 to 165 and ending at the stop codon found at nucleotidepositions 532 to 534 (FIG. 269; SEQ ID NO:374). The predictedpolypeptide precursor (FIG. 270, SEQ ID NO:375) is 123 amino acids long.PRO1158 has a calculated molecular weight of approximately 13,113daltons and an estimated pI of approximately 8.53. Additional featuresinclude a signal peptide sequence at about amino acids 1–19, atransmembrane domain at about amino acids 56–80, and a potentialN-glycosylation site at about amino acids 36–39. Clone DNA60625-1507 wasdeposited with the ATCC on Jun. 16, 1998 and is assigned ATCC depositno. 209975.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 270 (SEQ ID NO:375), revealed some homology between thePRO1158 amino acid sequence and the following Dayhoff sequences:ATAC00310510F18A8.10, P_R85151, PHS2_SOLTU, RNMHCIBAC_(—)1,RNALFMHC_(—)1, 168771, RNRT1A10G_(—)1, PTPA_HUMAN, HUMGACA_(—)1, andCHKPTPA_(—)1.

Example 121 Isolation of cDNA Clones Encoding Human PRO1159

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single EST cluster sequence from the Incytedatabase. This EST cluster sequence was then compared to a variety ofexpressed sequence tag (EST) databases which included public ESTdatabases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ®,Incyte Pharmaceuticals, Palo Alto, Calif.) to identify existinghomologies. The homology search was performed using the computer programBLAST or BLAST2 (Altshul et al., Methods in Enzymology 266:460–480(1996)). Those comparisons resulting in a BLAST score of 70 (or in somecases 90) or greater that did not encode known proteins were clusteredand assembled into a consensus DNA sequence with the program “phrap”(Phil Green, University of Washington, Seattle, Wash.). The consensussequence obtained therefrom is herein-designated DNA57221.

In light of an observed sequence homology between the DNA57221 consensussequence and an EST sequence encompassed within the Incyte EST clone no.376776, the Incyte EST clone 376776 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.271 and is herein designated as DNA60627-1508.

Clone DNA60627-1508 contains a single open reading frame with anapparent translational initiation site at nucleotide positions 92–94 andending at the stop codon at nucleotide positions 362–364 (FIG. 271). Thepredicted polypeptide precursor is 90 amino acids long (FIG. 272). Thefull-length PRO1159 protein shown in FIG. 272 has an estimated molecularweight of about 9,840 daltons and a pI of about 10.13. Analysis of thefull-length PRO1159 sequence shown in FIG. 272 (SEQ ID NO:377) evidencesthe presence of the following: a signal peptide from about amino acid 1to about amino acid 15 and a potential N-glycosylation site from aboutamino acid 38 to about amino acid 41. Clone DNA60627-1508 has beendeposited with ATCC on Aug. 4, 1998 and is assigned ATCC deposit no.203092.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 272 (SEQ ID NO:377), evidenced significant homologybetween the PRO1159 amino acid sequence and the following Dayhoffsequences: AF016494_(—)6, AF036708_(—)20, DSSCUTE_(—)1, D89100_(—)1,S28060, MEFA_XENLA, AF020798_(—)12, G70065, E64423, JQ2005.

Example 122 Isolation of cDNA Clones Encoding Human PRO1124

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single EST cluster sequence from the Incytedatabase. This EST cluster sequence was then compared to a variety ofexpressed sequence tag (EST) databases which included public ESTdatabases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ®,Incyte Pharmaceuticals, Palo Alto, Calif.) to identify existinghomologies. The homology search was performed using the computer programBLAST or BLAST2 (Altshul et al., Methods in Enzymology 266:460–480(1996)). Those comparisons resulting in a BLAST score of 70 (or in somecases 90) or greater that did not encode known proteins were clusteredand assembled into a consensus DNA sequence with the program “phrap”(Phil Green, University of Washington, Seattle, Wash.). The consensussequence obtained therefrom is herein designated DNA56035.

In light of an observed sequence homology between the DNA56035 consensussequence and an EST sequence encompassed within the Incyte EST clone no.2767646, the Incyte EST clone 2767646 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.273 and is herein designated as DNA60629-1481.

The full length clone shown in FIG. 273 contained a single open readingframe with an apparent translational initiation site at nucleotidepositions 25–27 and ending at the stop codon found at nucleotidepositions 2782–2784 (FIG. 273; SEQ ID NO:378). The predicted polypeptideprecursor (FIG. 274, SEQ ID NO:379) is 919 amino acids long. PRO1124 hasa calculated molecular weight of approximately 101,282 daltons and anestimated pI of approximately 5.37. Clone DNA60629-1481 has beendeposited with the ATCC and is assigned ATCC deposit no. 209979. It isunderstood that the deposited clone has the actual sequence, whereasonly representations based on current sequencing techniques which mayinclude normal and minor errors, are provided herein.

Based on a WU-BLAST2 sequence alignment analysis of the full-lengthsequence, PRO1124 shows significant amino acid sequence identity to achloride channel protein and to ECAM-1. Specifically, the followingDayhoff designations were identified as having sequence identity withPRO1124: ECLC_BOVIN, AF001261_(—)1, P_W06548, SSC6A10_(—b 1),AF004355_(—)1, S76691, AF017642, BYU06866_(—)2, CSA_DICDI andSAU47139_(—)2.

Example 123 Isolation of cDNA Clones Encoding Human PRO1287

An expressed sequence tag (EST) DNA database (LIFESEQ®, IncytePharmaceuticals, Palo Alto, Calif.) was searched and an EST wasidentified which showed homology to the fringe protein. This ESTsequence was then compared to various EST databases including public ESTdatabases (e.g., GenBank), and a proprietary EST database (LIFESEQ®,Incyte Pharmaceuticals, Palo Alto, Calif.) to identify homologous ESTsequences. The comparison was performed using the computer program BLASTor BLAST2 [Altschul et al., Methods in Enzymology, 266:460–480 (1996)].Those comparisons resulting in a BLAST score of 70 (or in some cases,90) or greater that did not encode known proteins were clustered andassembled into a consensus DNA sequence with the program “phrap” (PhilGreen, University of Washington, Seattle, Wash.). This consensussequence obtained is herein designated DNA40568.

Based on the DNA40568 consensus sequence, oligonucleotides weresynthesized: 1) to identify by PCR a cDNA library that contained thesequence of interest, and 2) for use as probes to isolate a clone of thefull-length coding sequence for PRO1287. Forward and reverse PCR primersgenerally range from 20 to 30 nucleotides and are often designed to givea PCR product of about 100–1000 bp in length. The probe sequences aretypically 40–55 bp in length. In some cases, additional oligonucleotidesare synthesized when the consensus sequence is greater than about 1–1.5kbp. In order to screen several libraries for a full-length clone, DNAfrom the libraries was screened by PCR amplification, as per Ausubel etal., Current Protocols in Molecular Biology, supra, with the PCR primerpair. A positive library was then used to isolate clones encoding thegene of interest using the probe oligonucleotide and one of the primerpairs.

PCR primers (forward and reverse) were synthesized:

forward PCR primer 5′-CTCGGGGAAAGGGACTTGATGTTGG-3′ (SEQ ID NO:382)reverse PCR primer 1 5′-GCGAAGGTGAGCCTCTATCTCGTGCC-3′ (SEQ ID NO:383)reverse PCR primer 2 5′-CAGCCTACACGTATTGAGG-3′ (SEQ ID NO:384)Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the consensus DNA40568 sequence which had the followingnucleotide sequenceHybridization Probe

-   5′-CAGTCAGTACAATCCTGGCATAATATACGGCCACCATGATGCAGTCCC-3′ (SEQ ID    NO:385).

In order to screen several libraries for a source of a full-lengthclone, DNA from the libraries was screened by PCR amplification with thePCR primer pairs identified above. A positive library was then used toisolate clones encoding the PRO1287 gene using the probe oligonucleotideand one of the PCR primers.

RNA for construction of the cDNA libraries was isolated from human bonemarrow tissue. The cDNA libraries used to isolated the cDNA clones wereconstructed by standard methods using commercially available reagentssuch as those from Invitrogen, San Diego, Calif. The cDNA was primedwith oligo dT containing a NotI site, linked with blunt to SalIhemikinased adaptors, cleaved with NotI, sized appropriately by gelelectrophoresis, and cloned in a defined orientation into a suitablecloning vector (such as pRKB or PRKD; pRK5B is a precursor of pRK5D thatdoes not contain the SfiI site; see, Holmes et al., Science,253:1278–1280 (1991)) in the unique XhoI and NotI sites.

DNA sequencing of the clones isolated as described above gave thefull-length DNA sequence for PRO1287 (designated herein as DNA61755-1554[FIG. 275, SEQ ID NO:380]) and the derived protein sequence for PRO1287.

The entire nucleotide sequence of DNA61755-1554 is shown in FIG. 275(SEQ ID NO:380). The full length clone contained a single open readingframe with an apparent translational initiation site at nucleotidepositions 655–657 and a stop signal at nucleotide positions 2251–2253(FIG. 275, SEQ ID NO:380). The predicted polypeptide precursor is 532amino acids long, has a calculated molecular weight of approximately61,351 daltons and an estimated pI of approximately 8.77. Analysis ofthe full-length PRO1287 sequence shown in FIG. 276 (SEQ ID NO:381)evidences the presence of the following: a signal peptide from aboutamino acid 1 to about amino acid 27 and potential N-glycosylation sitesfrom about amino acid 315 to about amino acid 318 and from about aminoacid 324 to about amino acid 327. Clone DNA61755-1554 has been depositedwith ATCC on Aug. 11, 1998 and is assigned ATCC deposit no. 203112.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 276 (SEQ ID NO:381), evidenced significant homologybetween the PRO1287 amino acid sequence and the following Dayhoffsequences: CET24D1_(—)1, EZRI_BOVIN, GGU19889_(—)1, CC3_YEAST, S74244,NALS_MOUSE, MOES_PIG, S28660, S44860 and YNA4_CAEEL.

Example 124 Isolation of cDNA Clones Encoding Human PRO1312

DNA55773 was identified in a human fetal kidney cDNA library using ayeast screen that preferentially represents the 5′ ends of the primarycDNA clones. Based on the DNA55773 sequence, oligonucleotides weresynthesized for use as probes to isolate a clone of the full-lengthcoding sequence for PRO1312.

The full length DNA61873-1574 clone shown in FIG. 277 (SEQ ID NO:386)contained a single open reading frame with an apparent translationalinitiation site at nucleotide positions 7–9 and ending at the stop codonfound at nucleotide positions 643–645. The predicted polypeptideprecursor is 212 amino acids long (FIG. 278, SEQ ID NO:387). PRO1312 hasa calculated molecular weight of approximately 24,024 daltons and anestimated pI of approximately 6.26. Other features include a signalpeptide at about amino acids 1–14; a transmembrane domain at about aminoacids 141–160, and potential N-glycosylation sites at about amino acids76–79 and 93–96.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 278 (SEQ ID NO:387), revealed some homology between thePRO1312 amino acid sequence and the following Dayhoff sequences:GCINTALPH_(—)1, GIBMUC1A_(—)1, P_R96298, AF001406_(—)1, PVU88874_(—)1,P_R85151, AF041409_(—)1, CELC50F2_(—)7, C45875, and AB009510_(—)21.

Clone DNA61873-1574 has been deposited with ATCC and is assigned ATCCdeposit no. 203132.

Example 125 Isolation of cDNA Clones Encoding Human PRO1192

A consensus DNA sequence was assembled relative to other EST sequencesusing phrap as described in Example 1 above. This consensus sequence isdesignated herein DNA35924. Based on the DNA35924 consensus sequence,oligonucleotides were synthesized: 1) to identify by PCR a cDNA librarythat contained the sequence of interest, and 2) for use as probes toisolate a clone of the full-length coding sequence for PRO1192.

PCR primers (forward and reverse) were synthesized:

forward PCR primer: 5′-CCGAGGCCATCTAGAGGCCAGAGC-3′ (SEQ ID NO:390)reverse PCR primer: 5′-ACAGGCAGAGCCAATGGCCAGAGC-3′ (SEQ ID NO:391).

Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the consensus DNA35924 sequence which had the followingnucleotide sequence:

Hybridization Probe

-   5′-GAGAGGACTGCGGGAGTTTGGGACCTTTGTGCAGACGTGCTCATG-3′ (SEQ ID NO:392).

In order to screen several libraries for a source of a full-lengthclone, DNA from the libraries was screened by PCR amplification with thePCR primer pair identified above. A positive library was then used toisolate clones encoding the PRO1192 gene using the probe oligonucleotideand one of the PCR primers. RNA for construction of the cDNA librarieswas isolated from human fetal liver and spleen tissue.

DNA sequencing of the clones isolated as described above gave thefull-length DNA sequence for PRO1192 designated herein as DNA62814-1521and shown in FIG. 279 (SEQ ID NO:388); and the derived protein sequencefor PRO1192 which is shown in FIG. 280 (SEQ ID NO:389).

The entire coding sequence of PRO1192 is shown in FIG. 279 (SEQ IDNO:388). Clone DNA62814-1521 contains a single open reading frame withan apparent translational initiation site at nucleotide positions121–123 and an apparent stop codon at nucleotide positions 766–768. Thepredicted polypeptide precursor is 215 amino acids long. The predictedpolypeptide precursor has the following features: a signal peptide atabout amino acids 1–21; a transmembrane domain at about amino acids153–176; potential N-glycosylation sites at about amino acids 39–42 and118–121; and homology with myelin P0 proteins at about amino acids 27–68and 99–128 of FIG. 280. The full-length PRO1192 protein shown in FIG.280 has an estimated molecular weight of about 24,484 daltons and a pIof about 6.98.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 280 (SEQ ID NO:389), revealed homology between the PRO1192amino acid sequence and the following Dayhoff sequences: GEN12838,MYP0_HUMAN, AF049498_(—)1, GEN14531, P_W14146, HS46KDA_(—)1, CINB_RAT,OX2G_RAT, D87018_(—)1, and D86996_(—)2.

Clone DNA62814-1521 was deposited with the ATCC on Aug. 4, 1998, and isassigned ATCC deposit no. 203093.

Example 126 Isolation of cDNA Clones Encoding Human PRO1160

A consensus DNA sequence was assembled relative to other EST sequencesusing phrap as described in Example 1 above This consensus sequence isherein designated DNA40650. Based on the DNA40650 consensus sequence,oligonucleotides were synthesized: 1) to identify by PCR a cDNA librarythat contained the sequence of interest, and 2) for use as probes toisolate a clone of the full-length coding sequence for PRO1160.

PCR primers (forward and reverse) were synthesized:

forward PCR primer 5′-GCTCCCTGATCTTCATGTCACCACC-3′ (SEQ ID NO:395)reverse PCR primer 5′-CAGGGACACACTCTACCATTCGGGAG-3′ (SEQ ID NO:396)Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the consensus DNA40650 sequence which had the followingnucleotide sequenceHybridization Probe

-   5′-CCATCTTTCTGGTCTCTGCCCAGAATCCGACAACAGCTGCTC-3′ (SEQ ID NO:397)

In order to screen several libraries for a source of a full-lengthclone, DNA from the libraries was screened by PCR amplification with thePCR primer pair identified above. A positive library was then used toisolate clones encoding the PRO1160 gene using the probe oligonucleotideand one of the PCR primers. RNA for construction of the cDNA librarieswas isolated from human breast tissue.

DNA sequencing of the clones isolated as described above gave thefull-length DNA sequence for PRO1160 (designated herein as DNA62872-1509[FIG. 281, SEQ ID NO:393]) and the derived protein sequence for PRO1160.

The entire nucleotide sequence of DNA62872-1509 is shown in FIG. 281(SEQ ID NO:393). Clone DNA62872-1509 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 40–42 and ending at the stop codon at nucleotide positions310–312 (FIG. 281). The predicted polypeptide precursor is 90 aminoacids long (FIG. 282). The full-length PRO1160 protein shown in FIG. 282has an estimated molecular weight of about 9,039 daltons and a pI ofabout 4.37. Analysis of the full-length PRO1160 sequence shown in FIG.282 (SEQ ID NO:394) evidences the presence of the following: a signalpeptide from about amino acid 1 to about amino acid 19 and a proteinkinase C phosphorylation site from about amino acid 68 to about aminoacid 70. Clone DNA62872-1509 has been deposited with ATCC on Aug. 4,1998 and is assigned ATCC deposit no. 203100.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 282 (SEQ ID NO:394), evidenced significant homologybetween the PRO1160 amino acid sequence and the following Dayhoffsequences: B30305, GEN13490, I53641, S53363, HA34_BRELC, SP96_DICDI,S36326, SSU51197_(—)10, MUC1_XENLA, TCU32448_(—)1 and AF000409_(—)1.

Example 127 Isolation of cDNA Clones Encoding Human PRO1187

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single EST cluster sequence from the Incytedatabase. This EST cluster sequence was then compared to a variety ofexpressed sequence tag (EST) databases which included public ESTdatabases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ®,Incyte Pharmaceuticals, Palo Alto, Calif.) to identify existinghomologies. The homology search was performed using the computer programBLAST or BLAST2 (Altshul et al., Methods in Enzymology 266:460–480(1996)). Those comparisons resulting in a BLAST score of 70 (or in somecases 90) or greater that did not encode known proteins were clusteredand assembled into a consensus DNA sequence with the program “phrap”(Phil Green, University of Washington, Seattle, Wash.). The consensussequence obtained therefrom is herein designated DNA57726.

In light of an observed sequence homology between the DNA57726 consensussequence and an EST sequence encompassed within the Incyte EST clone no.358563, the Incyte EST clone 358563 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.283 and is herein designated as DNA62876-1517.

The full length clone shown in FIG. 283 contained a single open readingframe with an apparent translational initiation site at nucleotidepositions 121–123 and ending at the stop codon found at nucleotidepositions 481–483 (FIG. 283; SEQ ID NO:398). The predicted polypeptideprecursor (FIG. 284, SEQ ID NO:399) is 120 amino acids long. The signalpeptide is at about amino acids 1–17 of SEQ ID NO:399. PRO1187 has acalculated molecular weight of approximately 12,925 daltons and anestimated pI of approximately 9.46. Clone DNA62876-1517 was depositedwith the ATCC on Aug. 4, 1998 and is assigned ATCC deposit no. 203095.It is understood that the deposited clone contains the actual sequenceand that the representations herein may have minor sequencing errors.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 284 (SEQ ID NO:399), revealed some sequence identity (andtherefore some relation) between the PRO1187 amino acid sequence and thefollowing Dayhoff sequences: MGNENDOBX_(—)1, CELF41G3_(—)9, AMPG_STRLI,HSBBOVHERL_(—)2, LEEXTEN10_(—)1, AF029958_(—)1 and P_W04957.

Example 128 Isolation of cDNA Clones Encoding Human PRO1185

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single EST cluster sequence from the Incytedatabase. This EST cluster sequence was then compared to a variety ofexpressed sequence tag (EST) databases which included public ESTdatabases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ®,Incyte Pharmaceuticals, Palo Alto, Calif.) to identify existinghomologies. The homology search was performed using the computer programBLAST or BLAST2 (Altshul et al., Methods in Enzymology 266:460–480(1996)). Those comparisons resulting in a BLAST score of 70 (or in somecases 90) or greater that did not encode known proteins were clusteredand assembled into a consensus DNA sequence with the program “phrap”(Phil Green, University of Washington, Seattle, Wash.). The consensussequence obtained therefrom is herein designated DNA56426.

In light of an observed sequence homology between the DNA56426 consensussequence and an EST sequence encompassed within the Incyte EST clone no.3284411, the Incyte EST clone 3284411 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.285 and is herein designated as DNA62881-1515.

The full length DNA62881-1515 clone shown in FIG. 285 contained a singleopen reading frame with an apparent translational initiation site atnucleotide positions 4–6 and ending at the stop codon found atnucleotide positions 598–600 (FIG. 285; SEQ ID NO:400). The predictedpolypeptide precursor (FIG. 286, SEQ ID NO:401) is 198 amino acids long.The signal peptide is at about amino acids 1–21 of SEQ ID NO:401.PRO1185 has a calculated molecular weight of approximately 22,105daltons and an estimated pI of approximately 7.73. Clone DNA62881-1515has been deposited with the ATCC and is assigned ATCC deposit no.203096.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 286 (SEQ ID NO:401), revealed some sequence identitybetween the PRO1185 amino acid sequence and the following Dayhoffsequences: TUP1_YEAST, AF041382_(—)1, MAOM_SOLTU, SPPBPHU9_(—)1, I41024,EPCPLCFAIL_(—)1, HSPLEC_(—)1, YKL4_CAEEL, A44643, TGU65922_(—)1.

Example 129 Isolation of cDNA Clones Encoding Human PRO1345

A consensus DNA sequence was assembled relative to other EST sequencesusing phrap as described in Example 1 above. This consensus sequence isherein designated DNA47364. Based on the DNA47364 consensus sequence,oligonucleotides were synthesized: 1) to identify by PCR a cDNA librarythat contained the sequence of interest, and 2) for use as probes toisolate a clone of the full-length coding sequence for PRO1345.

PCR primers (forward and reverse) were synthesized:

forward PCR primer 5′-CCTGGTTATCCCCAGGAACTCCGAC-3′ (SEQ ID NO:404)reverse PCR primer 5′-CTCTTGCTGCTGCGACAGGCCTC-3′ (SEQ ID NO:405)Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the consensus DNA47364 sequence which had the followingnucleotide sequenceHybridization Probe

-   5′-CGCCCTCCAAGACTATGGTAAAAGGAGCCTGCCAGGTGTCAATGAC-3′ (SEQ ID NO:406)

In order to screen several libraries for a source of a full-lengthclone, DNA from the libraries was screened by PCR amplification with thePCR primer pair identified above. A positive library was then used toisolate clones encoding the PRO1345 gene using the probe oligonucleotideand one of the PCR primers. RNA for construction of the cDNA librarieswas isolated from human breast carcinoma tissue.

DNA sequencing of the clones isolated as described above gave thefull-length DNA sequence for PRO1345 (designated herein as DNA64852-1589[FIG. 287, SEQ ID NO:402]) and the derived protein sequence for PRO1345.

The entire nucleotide sequence of DNA64852-1589 is shown in FIG. 287(SEQ ID NO:402). Clone DNA64852-1589 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 7–9 or 34–36 and ending at the stop codon at nucleotidepositions 625–627 (FIG. 287). The predicted polypeptide precursor is 206amino acids long (FIG. 288). The full-length PRO1345 protein shown inFIG. 288 has an estimated molecular weight of about 23,190 daltons and apI of about 9.40. Analysis of the full-length PRO1345 sequence shown inFIG. 288 (SEQ ID NO:403) evidences the presence of the following: asignal peptide from about amino acid 1 to about amino acid 31 or fromabout amino acid 10 to about amino acid 31 and a C-type lectin domainsignature sequence from about amino acid 176 to about amino acid 190.Clone DNA64852-1589 has been deposited with ATCC on Aug. 18, 1998 and isassigned ATCC deposit no. 203127.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 288 (SEQ ID NO:403), evidenced significant homologybetween the PRO1345 amino acid sequence and the following Dayhoffsequences: BTU22298_(—)1, TETN_CARSP, TETN_HUMAN, MABA_RAT, S34198,P_W13144, MACMBPA_(—)1, A46274, PSPD_RAT AND P_R32188.

Example 130 Isolation of cDNA Clones Encoding Human PRO1245

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single EST cluster sequence from the Incytedatabase. This EST cluster sequence was then compared to a variety ofexpressed sequence tag (EST) databases which included public ESTdatabases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ®,Incyte Pharmaceuticals, Palo Alto, Calif.) to identify existinghomologies. The homology search was performed using the computer programBLAST or BLAST2 (Altshul et al., Methods in Enzymology 266:460–480(1996)). Those comparisons resulting in a BLAST score of 70 (or in somecases 90) or greater that did not encode known proteins were clusteredand assembled into a consensus DNA sequence with the program “phrap”(Phil Green, University of Washington, Seattle, Wash.). The consensussequence obtained therefrom is herein designated DNA56019.

In light of an observed sequence homology between the DNA56019 consensussequence and an EST sequence encompassed within the Incyte EST clone no.1327836, the Incyte EST clone 1327836 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.289 and is herein designated as DNA64884-1527.

The full length clone shown in FIG. 289 contained a single open readingframe with an apparent translational initiation site at nucleotidepositions 79–81 and ending at the stop codon found at nucleotidepositions 391–393 (FIG. 289; SEQ ID NO:407). The predicted polypeptideprecursor (FIG. 290, SEQ ID NO:408) is 104 amino acids long, with asignal peptide sequence at about amino acid 1 to about amino acid 18.PRO1245 has a calculated molecular weight of approximately 10,100daltons and an estimated pI of approximately 8.76.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 290 (SEQ ID NO:408), revealed some homology between thePRO1245 amino acid sequence and the following Dayhoff sequences:SYA_THETH, GEN11167, MTV044_(—)4, AB011151_(—)1, RLAJ2750_(—)3,SNELIPTRA_(—)1, S63624, C28391, A37907, and S14064.

Clone DNA64884-1245 was deposited with the ATCC on Aug. 25, 1998 and isassigned ATCC deposit no. 203155.

Example 131 Isolation of cDNA Clones Encoding Human PRO1358

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single EST cluster sequence from the Incytedatabase. This EST cluster sequence was then compared to a variety ofexpressed sequence tag (EST) databases which included public ESTdatabases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ®,Incyte Pharmaceuticals, Palo Alto, Calif.) to identify existinghomologies. The homology search was performed using the computer programBLAST or BLAST2 (Altshul et al., Methods in Enzymology 266:460–480(1996)). Those comparisons resulting in a BLAST score of 70 (or in somecases 90) or greater that did not encode known proteins were clusteredand assembled into a consensus DNA sequence with the program “phrap”(Phil Green, University of Washington, Seattle, Wash.).

In light of an observed sequence homology between the consensus sequenceand an EST sequence encompassed within the Incyte EST clone no. 88718,the Incyte EST clone 88718 was purchased and the cDNA insert wasobtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.291 and is herein designated as DNA64890-1612.

The full length clone shown in FIG. 291 contained a single open readingframe with an apparent translational initiation site at nucleotidepositions 86 through 88 and ending at the stop codon found at nucleotidepositions 1418 through 1420 (FIG. 291; SEQ ID NO:409). The predictedpolypeptide precursor (FIG. 292, SEQ ID NO:410) is 444 amino acids long.The signal peptide is at about amino acids 1–18 of SEQ ID NO:410.PRO1358 has a calculated molecular weight of approximately 50,719daltons and an estimated pI of approximately 8.82. Clone DNA64890-1612was deposited with the ATCC on Aug. 18, 1998 and is assigned ATCCdeposit no. 203131.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 292 (SEQ ID NO:410), revealed sequence identity betweenthe PRO1358 amino acid sequence and the following Dayhoff sequences:P_WO7607, AB000545_(—)1, AB000546_(—)1, A1AT_RAT, AB015164_(—)1,P_P50021, COTR_CAVPO, and HAMHPP_(—)1. The variants claimed in thisapplication exclude these sequences.

Example 132 Isolation of cDNA Clones Encoding Human PRO1195

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single EST cluster sequence from the Incytedatabase. This EST cluster sequence was then compared to a variety ofexpressed sequence tag (EST) databases which included public ESTdatabases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ®,Incyte Pharmaceuticals, Palo Alto, Calif.) to identify existinghomologies. The homology search was performed using the computer programBLAST or BLAST2 (Altshul et al., Methods in Enzymology 266:460–480(1996)). Those comparisons resulting in a BLAST score of 70 (or in somecases 90) or greater that did not encode known proteins were clusteredand assembled into a consensus DNA sequence with the program “phrap”(Phil Green, University of Washington, Seattle, Wash.). The consensussequence obtained therefrom is herein designated DNA55716.

In light of an observed sequence homology between the DNA55716 consensussequence and an EST sequence encompassed within the Incyte EST clone no.3252980, the Incyte EST clone 3252980 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.293 and is herein designated as DNA65412-1523.

The full length clone shown in FIG. 293 contained a single open readingframe with an apparent translational initiation site at nucleotidepositions 58–60 and ending at the stop codon found at nucleotidepositions 511–513 (FIG. 293; SEQ ID NO:411). The predicted polypeptideprecursor (FIG. 294, SEQ ID NO:412) is 151 amino acids long. The signalsequence is at about amino acids 1–22 of SEQ ID NO:412. PRO1195 has acalculated molecular weight of approximately 17,277 daltons and anestimated pI of approximately 5.33. Clone DNA65412-1523 was depositedwith the ATCC on Aug. 4, 1998 and is assigned ATCC deposit no. 203094.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 294 (SEQ ID NO:412), revealed some sequence identitybetween the PRO1195 amino acid sequence and the following Dayhoffsequences: MMU28486_(—)1, AF044205_(—)1, P_W31186, CELK03C7_(—)1,F69034, EF1A_METVA, AF024540_(—)1, SSU90353_(—)1, MRSP_STAAU andP_R97680.

Example 133 Isolation of cDNA Clones Encoding Human PRO1270

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single EST cluster sequence from the Incytedatabase. This EST cluster sequence was then compared to a variety ofexpressed sequence tag (EST) databases which included public ESTdatabases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ®,Incyte Pharmaceuticals, Palo Alto, Calif.) to identify existinghomologies. The homology search was performed using the computer programBLAST or BLAST2 (Altshul et al., Methods in Enzymology 266:460–480(1996)). Those comparisons resulting in a BLAST score of 70 (or in somecases 90) or greater that did not encode known proteins were clusteredand assembled into a consensus DNA sequence with the program “phrap”(Phil Green, University of Washington, Seattle, Wash.). The consensussequence obtained therefrom is herein designated DNA57951.

In light of an observed sequence homology between the DNA57951 consensussequence and an EST sequence encompassed within the Merck EST clone no.124878, the Merck EST clone 124878 was purchased and the cDNA insert wasobtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.295 and is herein designated as DNA66308-1537.

Clone DNA66308-1537 contains a single open reading frame with anapparent translational initiation site at nucleotide positions 103–105and ending at the stop codon at nucleotide positions 1042–1044 (FIG.295). The predicted polypeptide precursor is 313 amino acids long (FIG.296). The full-length PRO1270 protein shown in FIG. 296 has an estimatedmolecular weight of about 34,978 daltons and a pI of about 5.71.Analysis of the full-length PRO1270 sequence shown in FIG. 296 (SEQ IDNO:414) evidences the presence of the following: a signal peptide fromabout amino acid 1 to about amino acid 16, a potential N-glycosylationsite from about amino acid 163 to about amino acid 166 andglycosaminoglycan attachment sites from about amino acid 74 to aboutamino acid 77 and from about amino acid 289 to about amino acid 292.Clone DNA66308-1537 has been deposited with ATCC on Aug. 25, 1998 and isassigned ATCC deposit no. 203159.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 296 (SEQ ID NO:414), evidenced significant homologybetween the PRO1270 amino acid sequence and the following Dayhoffsequences: XLU86699_(—)1, S49589, FIBA_PARPA, FIBB_HUMAN, P_R47189,AF004326_(—)1, DRTENASCN_(—)1, AF004327_(—)1, P_W01411 and FIBG_BOVIN.

Example 134 Isolation of cDNA Clones Encoding Human PRO1271

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single EST cluster sequence from the Incytedatabase. This EST cluster sequence was then compared to a variety ofexpressed sequence tag (EST) databases which included public ESTdatabases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ®,Incyte Pharmaceuticals, Palo Alto, Calif.) to identify existinghomologies. The homology search was performed using the computer programBLAST or BLAST2 (Altshul et al., Methods in Enzymology 266:460–480(1996)). Those comparisons resulting in a BLAST score of 70 (or in somecases 90) or greater that did not encode known proteins were clusteredand assembled into a consensus DNA sequence with the program “phrap”(Phil Green, University of Washington, Seattle, Wash.). The consensussequence obtained therefrom is herein designated DNA57955.

In light of an observed sequence homology between the DNA57955 consensussequence and an EST sequence encompassed within the Merck EST clone no.AA625350, the Merck EST clone AA625350 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.297 and is herein designated as DNA66309-1538.

Clone DNA66309-1538 contains a single open reading frame with anapparent translational initiation site at nucleotide positions 94–96 andending at the stop codon at nucleotide positions 718–720 (FIG. 297). Thepredicted polypeptide precursor is 208 amino acids long (FIG. 298). Thefull-length PRO1271 protein shown in FIG. 298 has an estimated molecularweight of about 21,531 daltons and a pI of about 8.99. Analysis of thefull-length PRO1271 sequence shown in FIG. 298 (SEQ ID NO:416) evidencesthe presence of the following: a signal peptide from about amino acid 1to about amino acid 31 and a transmembrane domain from about amino acid166 to about amino acid 187. Clone DNA66309-1538 has been deposited withATCC on Sep. 15, 1998 and is assigned ATCC deposit no. 203235.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 298 (SEQ ID NO:416), evidenced significant homologybetween the PRO1271 amino acid sequence and the following Dayhoffsequences: S57180, S63257, AGA1_YEAST, BPU43599_(—)1, YS8A_CAEEL,S67570, LSU54556_(—)2, S70305, VGLX_HSVEB, and D88733_(—)1.

Example 135 Isolation of cDNA Clones Encoding Human PRO1375

A Merck/Wash. U. database was searched and a Merck EST was identified.This sequence was then put in a program which aligns it with othersequences from the Swiss-Prot public database, public EST databases(e.g., GenBank, Merck/Wash. U.), and a proprietary EST database(LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, Calif.). The search wasperformed using the computer program BLAST or BLAST2 [Altschul et al.,Methods in Enzymology, 266:460–480 (1996)] as a comparison of theextracellular domain (ECD) protein sequences to a 6 frame translation ofthe EST sequences. Those comparisons resulting in a BLAST score of 70(or in some cases, 90) or greater that did not encode known proteinswere clustered and assembled into consensus DNA sequences with theprogram “phrap” (Phil Green, University of Washington, Seattle, Wash.).

A consensus DNA sequence was assembled relative to other EST sequencesusing phrap. This consensus sequence is designated herein “DNA67003”.

Based on the DNA67003 consensus sequence, the nucleic acid (SEQ IDNO:417) was identified in a human pancreas library. DNA sequencing ofthe clone gave the full-length DNA sequence for PRO1375 and the derivedprotein sequence for PRO1375.

The entire coding sequence of PRO1375 is shown in FIG. 299 (SEQ IDNO:417). Clone DNA67004-1614 contains a single open reading frame withan apparent translational initiation site at nucleotide positions104–106 and an apparent stop codon at nucleotide positions 698–700 ofSEQ ID NO:417. The predicted polypeptide precursor is 198 amino acidslong. The transmembrane domains are at about amino acids 11–28 (type II)and 103–125 of SEQ ID NO:418. Clone DNA67004-1614 has been depositedwith ATCC and is assigned ATCC deposit no. 203115. The full-lengthPRO1375 protein shown in FIG. 300 has an estimated molecular weight ofabout 22,531 daltons and a pI of about 8.47.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 300 (SEQ ID NO:418), revealed sequence identity betweenthe PRO1375 amino acid sequence and the following Dayhoff sequences:AF026198_(—)5, CELR12C12_(—)5, S73465, Y011_MYCPN, S64538_(—)1, P_P8150,MUVSHPO10_(—)1, VSH_MUMPL and CVU59751_(—)5.

Example 136 Isolation of cDNA Clones Encoding Human PRO1385

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single EST cluster sequence from the Incytedatabase. This EST cluster sequence was then compared to a variety ofexpressed sequence tag (EST) databases which included public ESTdatabases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ®,Incyte Pharmaceuticals, Palo Alto, Calif.) to identify existinghomologies. The homology search was performed using the computer programBLAST or BLAST2 (Altshul et al., Methods in Enzymology 266:460–480(1996)). Those comparisons resulting in a BLAST score of 70 (or in somecases 90) or greater that did not encode known proteins were clusteredand assembled into a consensus DNA sequence with the program “phrap”(Phil Green, University of Washington, Seattle, Wash.). The consensussequence obtained therefrom is herein designated DNA57952.

In light of an observed sequence homology between the DNA57952 consensussequence and an EST sequence encompassed within the Incyte EST clone no.3129630, the Incyte EST clone 3129630 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.301 and is herein designated as DNA68869-1610.

Clone DNA68869-1610 contains a single open reading frame with anapparent translational initiation site at nucleotide positions 26–28 andending at the stop codon at nucleotide positions 410–412 (FIG. 301). Thepredicted polypeptide precursor is 128 amino acids long (FIG. 302). Thefull-length PRO1385 protein shown in FIG. 302 has an estimated molecularweight of about 13,663 daltons and a pI of about 10.97. Analysis of thefull-length PRO1385 sequence shown in FIG. 302 (SEQ ID NO:420) evidencesthe presence of the following: a signal peptide from about amino acid 1to about amino acid 28, and glycosylaminoglycan attachment sites fromabout amino acid 82 to about amino acid 85 and from about amino acid 91to about amino acid 94. Clone DNA68869-1610 has been deposited with ATCCon Aug. 25, 1998 and is assigned ATCC deposit no. 203164.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 302 (SEQ ID NO:420), evidenced low homology between thePRO1385 amino acid sequence and the following Dayhoff sequences:CELT14A8_(—)1, LMNACHRA1_(—)1, HXD9_HUMAN, CHKCMLF_(—)1, HS5PP34_(—)2,DMDRING_(—)1, A37107_(—)1, MMLUNGENE_(—)1, PUM_DROME and DMU25117_(—)1.

Example 137 Isolation of cDNA Clones Encoding Human PRO1387

Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single EST cluster sequence from the Incytedatabase. This EST cluster sequence was then compared to a variety ofexpressed sequence tag (EST) databases which included public ESTdatabases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ®,Incyte Pharmaceuticals, Palo Alto, Calif.) to identify existinghomologies. The homology search was performed using the computer programBLAST or BLAST2 (Altshul et al., Methods in Enzymology 266:460–480(1996)). Those comparisons resulting in a BLAST score of 70 (or in somecases 90) or greater that did not encode known proteins were clusteredand assembled into a consensus DNA sequence with the program “phrap”(Phil Green, University of Washington, Seattle, Wash.). The consensussequence obtained therefrom is herein designated DNA56259.

In light of an observed sequence homology between the DNA56259 consensussequence and an EST sequence encompassed within the Incyte EST clone no.3507924, the Incyte EST clone 3507924 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.303 and is herein designated as DNA68872-1620.

Clone DNA68872-1620 contains a single open reading frame with anapparent translational initiation site at nucleotide positions 85–87 andending at the stop codon at nucleotide positions 1267–1269 (FIG. 303).The predicted polypeptide precursor is 394 amino acids long (FIG. 304).The full-length PRO1387 protein shown in FIG. 304 has an estimatedmolecular weight of about 44,339 daltons and a pI of about 7.10.Analysis of the full-length PRO1387 sequence shown in FIG. 304 (SEQ IDNO:422) evidences the presence of the following: a signal peptide fromabout amino acid 1 to about amino acid 19, a transmembrane domain fromabout amino acid 275 to about amino acid 296, potential N-glycosylationsites from about amino acid 76 to about amino acid 79, from about aminoacid 231 to about amino acid 234, from about amino acid 302 to aboutamino acid 305, from about amino acid 307 to about amino acid 310 andfrom about amino acid 376 to about amino acid 379, and amino acidsequence blocks having homology to myelin p0 protein from about aminoacid 210 to about amino acid 239 and from about amino acid 92 to aboutamino acid 121. Clone DNA68872-1620 has been deposited with ATCC on Aug.25, 1998 and is assigned ATCC deposit no. 203160.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 304 (SEQ ID NO:422), evidenced significant homologybetween the PRO1387 amino acid sequence and the following Dayhoffsequences: P_W36955, MYP0_HETFR, HS46KDA_(—)1, AF049498_(—)1,MYO0_HUMAN, AF030454_(—)1, A53268, SHPTCRA_(—)1, P_W14146 and GEN12838.

Example 138 Isolation of cDNA Clones Encoding Human PRO1384

A consensus DNA sequence was assembled relative to other EST sequencesusing phrap as described in Example 1 above. This consensus sequence isherein designated DNA54192. Based on the DNA54192 sequence,oligonucleotides were synthesized: 1) to identify by PCR a cDNA librarythat contained the sequence of interest, and 2) for use as probes toisolate a clone of the full-length coding sequence for PRO1384.

PCR primers (forward and reverse) were synthesized:

forward PCR primer 5′-TGCAGCCCCTGTGACACAAACTGG-3′ (SEQ ID NO:425)reverse PCR primer 5′-CTGAGATAACCGAGCCATCCTCCCAC-3′ (SEQ ID NO:426)

Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the DNA54192 sequence which had the followingnucleotide sequence:

Hybridization Probe

-   5′-GGAGATAGCTGCTATGGGTTCTTCAGGCACAACTTAACATGGGAAG-3′ (SEQ ID NO:427)

In order to screen several libraries for a source of a full-lengthclone, DNA from the libraries was screened by PCR amplification with thePCR primer pair identified above. A positive library was then used toisolate clones encoding the PRO1384 gene using the probe oligonucleotideand one of the PCR primers. RNA for construction of the cDNA librarieswas isolated from human fetal liver.

DNA sequencing of the clones isolated as described above gave thefull-length DNA sequence for PRO1384 (designated herein as DNA71159-1617[FIG. 305, SEQ ID NO:423]; and the derived protein sequence for PRO1384.

The entire coding sequence of PRO1384 is shown in FIG. 305 (SEQ IDNO:423). Clone DNA71159-1617 contains a single open reading frame withan apparent translational initiation site at nucleotide positions182–184 and an apparent stop codon at nucleotide positions 869–871. Thepredicted polypeptide precursor is 229 amino acids long. The full-lengthPRO1384 protein shown in FIG. 306 has an estimated molecular weight ofabout 26,650 daltons and a pI of about 8.76. Additional features includea type II transmembrane domain at about amino acids 32–57, and potentialN-glycosylation sites at about amino acids 68–71, 120–123, and 134–137.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usinga WU-BLAST2 sequence alignment analysis of the full-length sequenceshown in FIG. 306 (SEQ ID NO:424), revealed homology between the PRO1384amino acid sequence and the following Dayhoff sequences: AF054819_(—)1,HSAJ16871, AF009511_(—)1, AB010710_(—)1, GEN13595, HSAJ673_(—)1,GEN13961, AB005900_(—)1, LECH_CHICK, AF021349_(—)1, and NK13_RAT.

Clone DNA71159-1617 has been deposited with ATCC and is assigned ATCCdeposit no. 203135.

Example 139 Use of PRO as a Hybridization Probe

The following method describes use of a nucleotide sequence encoding PROas a hybridization probe.

DNA comprising the coding sequence of full-length or mature PRO asdisclosed herein is employed as a probe to screen for homologous DNAs(such as those encoding naturally-occurring variants of PRO) in humantissue cDNA libraries or human tissue genomic libraries.

Hybridization and washing of filters containing either library DNAs isperformed under the following high stringency conditions. Hybridizationof radiolabeled PRO-derived probe to the filters is performed in asolution of 50% formamide, 5×SSC, 0.1% SDS, 0.1% sodium pyrophosphate,50 mM sodium phosphate, pH 6.8, 2×Denhardt's solution, and 10% dextransulfate at 42° C. for 20 hours. Washing of the filters is performed inan aqueous solution of 0.1×SSC and 0.1% SDS at 42° C.

DNAs having a desired sequence identity with the DNA encodingfull-length native sequence PRO can then be identified using standardtechniques known in the art.

Example 140 Expression of PRO in E. coli

This example illustrates preparation of an unglycosylated form of PRO byrecombinant expression in E. coli.

The DNA sequence encoding PRO is initially amplified using selected PCRprimers. The primers should contain restriction enzyme sites whichcorrespond to the restriction enzyme sites on the selected expressionvector. A variety of expression vectors may be employed. An example of asuitable vector is pBR322 (derived from E. coli; see Bolivar et al.,Gene, 2:95 (1977)) which contains genes for ampicillin and tetracyclineresistance. The vector is digested with restriction enzyme anddephosphorylated. The PCR amplified sequences are then ligated into thevector. The vector will preferably include sequences which encode for anantibiotic resistance gene, a trp promoter, a polyhis leader (includingthe first six STII codons, polyhis sequence, and enterolinase cleavagesite), the PRO coding region, lambda transcriptional terminator, and anargu gene.

The ligation mixture is then used to transform a selected E. coli strainusing the methods described in Sambrook et al., supra. Transformants areidentified by their ability to grow on LB plates and antibioticresistant colonies are then selected. Plasmid DNA can be isolated andconfirmed by restriction analysis and DNA sequencing.

Selected clones can be grown overnight in liquid culture medium such asLB broth supplemented with antibiotics. The overnight culture maysubsequently be used to inoculate a larger scale culture. The cells arethen grown to a desired optical density, during which the expressionpromoter is turned on.

After culturing the cells for several more hours, the cells can beharvested by centrifugation. The cell pellet obtained by thecentrifugation can be solubilized using various agents known in the art,and the solubilized PRO protein can then be purified using a metalchelating column under conditions that allow tight binding of theprotein.

PRO may be expressed in E. coli in a poly-His tagged form, using thefollowing procedure. The DNA encoding PRO is initially amplified usingselected PCR primers. The primers will contain restriction enzyme siteswhich correspond to the restriction enzyme sites on the selectedexpression vector, and other useful sequences providing for efficientand reliable translation initiation, rapid purification on a metalchelation column, and proteolytic removal with enterokinase. ThePCR-amplified, poly-His tagged sequences are then ligated into anexpression vector, which is used to transform an E. coli host based onstrain 52 (W3110 fuhA(tonA) Ion galE rpoHts(htpRts) clpP(lacIq).Transformants are first grown in LB containing 50 mg/ml carbenicillin at30° C. with shaking until an O.D. 600 of 3–5 is reached. Cultures arethen diluted 50–100 fold into CRAP media (prepared by mixing 3.57 g(NH₄)₂SO₄, 0.71 g sodium citrate·2H2O, 1.07 g KCl, 5.36 g Difco yeastextract, 5.36 g Sheffield hycase SF in 500 mL water, as well as 110 mMMPOS, pH 7.3, 0.55% (w/v) glucose and 7 mM MgSO₄) and grown forapproximately 20–30 hours at 30° C. with shaking. Samples are removed toverify expression by SDS-PAGE analysis, and the bulk culture iscentrifuged to pellet the cells. Cell pellets are frozen untilpurification and refolding.

E. coli paste from 0.5 to 1 L fermentations (6–10 g pellets) isresuspended in 10 volumes (w/v) in 7 M guanidine, 20 mM Tris, pH 8buffer. Solid sodium sulfite and sodium tetrathionate is added to makefinal concentrations of 0.1M and 0.02 M, respectively, and the solutionis stirred overnight at 4° C. This step results in a denatured proteinwith all cysteine residues blocked by sulfitolization. The solution iscentrifuged at 40,000 rpm in a Beckman Ultracentifuge for 30 min. Thesupernatant is diluted with 3–5 volumes of metal chelate column buffer(6 M guanidine, 20 mM Tris, pH 7.4) and filtered through 0.22 micronfilters to clarify. The clarified extract is loaded onto a 5 ml QiagenNi-NTA metal chelate column equilibrated in the metal chelate columnbuffer. The column is washed with additional buffer containing 50 mMimidazole (Calbiochem, Utrol grade), pH 7.4. The protein is eluted withbuffer containing 250 mM imidazole. Fractions containing the desiredprotein are pooled and stored at 4° C. Protein concentration isestimated by its absorbance at 280 nm using the calculated extinctioncoefficient based on its amino acid sequence.

The proteins are refolded by diluting the sample slowly into freshlyprepared refolding buffer consisting of: 20 mM Tris, pH 8.6, 0.3 M NaCl,2.5 M urea, 5 mM cysteine, 20 mM glycine and 1 mM EDTA. Refoldingvolumes are chosen so that the final protein concentration is between 50to 100 micrograms/ml. The refolding solution is stirred gently at 4° C.for 12–36 hours. The refolding reaction is quenched by the addition ofTFA to a final concentration of 0.4% (pH of approximately 3). Beforefurther purification of the protein, the solution is filtered through a0.22 micron filter and acetonitrile is added to 2–10% finalconcentration. The refolded protein is chromatographed on a Poros Ri/Hreversed phase column using a mobile buffer of 0.1% TFA with elutionwith a gradient of acetonitrile from 10 to 80%. Aliquots of fractionswith A280 absorbance are analyzed on SDS polyacrylamide gels andfractions containing homogeneous refolded protein are pooled. Generally,the properly refolded species of most proteins are eluted at the lowestconcentrations of acetonitrile since those species are the most compactwith their hydrophobic interiors shielded from interaction with thereversed phase resin. Aggregated species are usually eluted at higheracetonitrile concentrations. In addition to resolving misfolded forms ofproteins from the desired form, the reversed phase step also removesendotoxin from the samples.

Fractions containing the desired folded PRO polypeptide are pooled andthe acetonitrile removed using a gentle stream of nitrogen directed atthe solution. Proteins are formulated into 20 mM Hepes, pH 6.8 with 0.14M sodium chloride and 4% mannitol by dialysis or by gel filtration usingG25 Superfine (Pharmacia) resins equilibrated in the formulation bufferand sterile filtered.

Many of the PRO polypeptides disclosed herein were successfullyexpressed as described above.

Example 141 Expression of PRO in Mammalian Cells

This example illustrates preparation of a potentially glycosylated formof PRO by recombinant expression in mammalian cells.

The vector, pRK5 (see EP 307,247, published Mar. 15, 1989), is employedas the expression vector. Optionally, the PRO DNA is ligated into pRK5with selected restriction enzymes to allow insertion of the PRO DNAusing ligation methods such as described in Sambrook et al., supra. Theresulting vector is called pRK5-PRO.

In one embodiment, the selected host cells may be 293 cells. Human 293cells (ATCC CCL 1573) are grown to confluence in tissue culture platesin medium such as DMEM supplemented with fetal calf serum andoptionally, nutrient components and/or antibiotics. About 10 μg pRK5-PRODNA is mixed with about 1 μg DNA encoding the VA RNA gene [Thimmappayaet al., Cell, 31:543 (1982)] and dissolved in 500 μl of 1 mM Tris-HCl,0.1 mM EDTA, 0.227 M CaCl₂. To this mixture is added, dropwise, 500 μlof 50 mM HEPES (pH 7.35), 280 mM NaCl, 1.5 mM NaPO₄, and a precipitateis allowed to form for 10 minutes at 25° C. The precipitate is suspendedand added to the 293 cells and allowed to settle for about four hours at37° C. The culture medium is aspirated off and 2 ml of 20% glycerol inPBS is added for 30 seconds. The 293 cells are then washed with serumfree medium, fresh medium is added and the cells are incubated for about5 days.

Approximately 24 hours after the transfections, the culture medium isremoved and replaced with culture medium (alone) or culture mediumcontaining 200 μCi/ml ³⁵S-cysteine and 200 μCi/ml ³⁵S-methionine. Aftera 12 hour incubation, the conditioned medium is collected, concentratedon a spin filter, and loaded onto a 15% SDS gel. The processed gel maybe dried and exposed to film for a selected period of time to reveal thepresence of PRO polypeptide. The cultures containing transfected cellsmay undergo further incubation (in serum free medium) and the medium istested in selected bioassays.

In an alternative technique, PRO may be introduced into 293 cellstransiently using the dextran sulfate method described by Somparyrac etal., Proc. Natl. Acad. Sci., 12:7575 (1981). 293 cells are grown tomaximal density in a spinner flask and 700 μg pRK5-PRO DNA is added. Thecells are first concentrated from the spinner flask by centrifugationand washed with PBS. The DNA-dextran precipitate is incubated on thecell pellet for four hours. The cells are treated with 20% glycerol for90 seconds, washed with tissue culture medium, and re-introduced intothe spinner flask containing tissue culture medium, 5 μg/ml bovineinsulin and 0.1 μg/ml bovine transferrin. After about four days, theconditioned media is centrifuged and filtered to remove cells anddebris. The sample containing expressed PRO can then be concentrated andpurified by any selected method, such as dialysis and/or columnchromatography.

In another embodiment, PRO can be expressed in CHO cells. The pRK5-PROcan be transfected into CHO cells using known reagents such as CaPO₄ orDEAE-dextran. As described above, the cell cultures can be incubated,and the medium replaced with culture medium (alone) or medium containinga radiolabel such as ³⁵S-methionine. After determining the presence ofPRO polypeptide, the culture medium may be replaced with serum freemedium. Preferably, the cultures are incubated for about 6 days, andthen the conditioned medium is harvested. The medium containing theexpressed PRO can then be concentrated and purified by any selectedmethod.

Epitope-tagged PRO may also be expressed in host CHO cells. The PRO maybe subcloned out of the pRK5 vector. The subclone insert can undergo PCRto fuse in frame with a selected epitope tag such as a poly-his tag intoa Baculovirus expression vector. The poly-his tagged PRO insert can thenbe subcloned into a SV40 driven vector containing a selection markersuch as DHFR for selection of stable clones. Finally, the CHO cells canbe transfected (as described above) with the SV40 driven vector.Labeling may be performed, as described above, to verify expression. Theculture medium containing the expressed poly-His tagged PRO can then beconcentrated and purified by any selected method, such as byNi²⁺-chelate affinity chromatography.

PRO may also be expressed in CHO and/or COS cells by a transientexpression procedure or in CHO cells by another stable expressionprocedure.

Stable expression in CHO cells is performed using the followingprocedure. The proteins are expressed as an IgG construct(immunoadhesin), in which the coding sequences for the soluble forms(e.g. extracellular domains) of the respective proteins are fused to anIgGl constant region sequence containing the hinge, CH2 and CH2 domainsand/or is a poly-His tagged form.

Following PCR amplification, the respective DNAs are subcloned in a CHOexpression vector using standard techniques as described in Ausubel etal., Current Protocols of Molecular Biology, Unit 3.16, John Wiley andSons (1997). CHO expression vectors are constructed to have compatiblerestriction sites 5′ and 3′ of the DNA of interest to allow theconvenient shuttling of cDNA's. The vector used expression in CHO cellsis as described in Lucas et al., Nucl. Acids Res. 24:9 (1774–1779(1996), and uses the SV40 early promoter/enhancer to drive expression ofthe cDNA of interest and dihydrofolate reductase (DHFR). DHFR expressionpermits selection for stable maintenance of the plasmid followingtransfection.

Twelve micrograms of the desired plasmid DNA is introduced intoapproximately 10 million CHO cells using commercially availabletransfection reagents Superfect® (Quiagen), Dosper® or Fugene®(Boehringer Mannheim). The cells are grown as described in Lucas et al.,supra. Approximately 3×10⁻⁷ cells are frozen in an ampule for furthergrowth and production as described below.

The ampules containing the plasmid DNA are thawed by placement intowater bath and mixed by vortexing. The contents are pipetted into acentrifuge tube containing 10 mLs of media and centrifuged at 1000 rpmfor 5 minutes. The supernatant is aspirated and the cells areresuspended in 10 mL of selective media (0.2 μm filtered PS20 with 5%0.2 μm diafiltered fetal bovine serum). The cells are then aliquotedinto a 100 mL spinner containing 90 mL of selective media. After 1–2days, the cells are transferred into a 250 mL spinner filled with 150 mLselective growth medium and incubated at 37° C. After another 2–3 days,250 mL, 500 and 2000 mL spinners are seeded with 3×10⁵ cells/mL. Thecell media is exchanged with fresh media by centrifugation andresuspension in production medium. Although any suitable CHO media maybe employed, a production medium described in U.S. Pat. No. 5,122,469,issued Jun. 16, 1992 may actually be used. A 3 L production spinner isseeded at 1.2×10⁶ cells/mL. On day 0, the cell number pH ie determined.On day 1, the spinner is sampled and sparging with filtered air iscommenced. On day 2, the spinner is sampled, the temperature shifted to33° C., and 30 mL of 500 g/L glucose and 0.6 mL of 10% antifoam (e.g.,35% polydimethylsiloxane emulsion, Dow Corning 365 Medical GradeEmulsion) taken. Throughout the production, the pH is adjusted asnecessary to keep it at around 7.2. After 10 days, or until theviability dropped below 70%, the cell culture is harvested bycentrifugation and filtering through a 0.22 μm filter. The filtrate waseither stored at 4° C. or immediately loaded onto columns forpurification.

For the poly-His tagged constructs, the proteins are purified using aNi-NTA column (Qiagen). Before purification, imidazole is added to theconditioned media to a concentration of 5 mM. The conditioned media ispumped onto a 6 ml Ni-NTA column equilibrated in 20 mM Hepes, pH 7.4,buffer containing 0.3 M NaCl and 5 mM imidazole at a flow rate of 4–5ml/min. at 4° C. After loading, the column is washed with additionalequilibration buffer and the protein eluted with equilibration buffercontaining 0.25 M imidazole. The highly purified protein is subsequentlydesalted into a storage buffer containing 10 mM Hepes, 0.14 M NaCl and4% mannitol, pH 6.8, with a 25 ml G25 Superfine (Pharmacia) column andstored at −80° C.

Immunoadhesin (Fc-containing) constructs are purified from theconditioned media as follows. The conditioned medium is pumped onto a 5ml Protein A column (Pharmacia) which had been equilibrated in 20 mM Naphosphate buffer, pH 6.8. After loading, the column is washedextensively with equilibration buffer before elution with 100 mM citricacid, pH 3.5. The eluted protein is immediately neutralized bycollecting 1 ml fractions into tubes containing 275 μL of 1 M Trisbuffer, pH 9. The highly purified protein is subsequently desalted intostorage buffer as described above for the poly-His tagged proteins. Thehomogeneity is assessed by SDS polyacrylamide gels and by N-terminalamino acid sequencing by Edman degradation.

Many of the PRO polypeptides disclosed herein were successfullyexpressed as described above.

Example 142 Expression of PRO in Yeast

The following method describes recombinant expression of PRO in yeast.

First, yeast expression vectors are constructed for intracellularproduction or secretion of PRO from the ADH2/GAPDH promoter. DNAencoding PRO and the promoter is inserted into suitable restrictionenzyme sites in the selected plasmid to direct intracellular expressionof PRO. For secretion, DNA encoding PRO can be cloned into the selectedplasmid, together with DNA encoding the ADH2/GAPDH promoter, a nativePRO signal peptide or other mammalian signal peptide, or, for example, ayeast alpha-factor or invertase secretory signal/leader sequence, andlinker sequences (if needed) for expression of PRO.

Yeast cells, such as yeast strain AB110, can then be transformed withthe expression plasmids described above and cultured in selectedfermentation media. The transformed yeast supernatants can be analyzedby precipitation with 10% trichloroacetic acid and separation bySDS-PAGE, followed by staining of the gels with Coomassie Blue stain.

Recombinant PRO can subsequently be isolated and purified by removingthe yeast cells from the fermentation medium by centrifugation and thenconcentrating the medium using selected cartridge filters. Theconcentrate containing PRO may further be purified using selected columnchromatography resins.

Many of the PRO polypeptides disclosed herein were successfullyexpressed as described above.

Example 143 Expression of PRO in Baculovirus-infected Insect Cells

The following method describes recombinant expression of PRO inBaculovirus-infected insect cells.

The sequence coding for PRO is fused upstream of an epitope tagcontained within a baculovirus expression vector. Such epitope tagsinclude poly-his tags and immunoglobulin tags (like Fc regions of IgG).A variety of plasmids may be employed, including plasmids derived fromcommercially available plasmids such as pVL1393 (Novagen). Briefly, thesequence encoding PRO or the desired portion of the coding sequence ofPRO such as the sequence encoding the extracellular domain of atransmembrane protein or the sequence encoding the mature protein if theprotein is extracellular is amplified by PCR with primers complementaryto the 5′ and 3′ regions. The 5′ primer may incorporate flanking(selected) restriction enzyme sites. The product is then digested withthose selected restriction enzymes and subcloned into the expressionvector.

Recombinant baculovirus is generated by co-transfecting the aboveplasmid and BaculoGold™ virus DNA (Pharmingen) into Spodoptera fugiperda(“Sf9”) cells (ATCC CRL 1711) using lipofectin (commercially availablefrom GIBCO-BRL). After 4–5 days of incubation at 28° C., the releasedviruses are harvested and used for further amplifications. Viralinfection and protein expression are performed as described by O'Reilleyet al., Baculovirus expression vectors: A Laboratory Manual, Oxford:Oxford University Press (1994).

Expressed poly-his tagged PRO can then be purified, for example, byNi²⁺-chelate affinity chromatography as follows. Extracts are preparedfrom recombinant virus-infected Sf9 cells as described by Rupert et al.,Nature, 362:175–179 (1993). Briefly, Sf9 cells are washed, resuspendedin sonication buffer (25 mL Hepes, pH 7.9; 12.5 mM MgCl₂; 0.1 mM EDTA;10% glycerol; 0.1% NP-40; 0.4 M KC1), and sonicated twice for 20 secondson ice. The sonicates are cleared by centrifugation, and the supernatantis diluted 50-fold in loading buffer (50 mM phosphate, 300 mM NaCl, 10%glycerol, pH 7.8) and filtered through a 0.45 μm filter. A Ni²⁺-NTAagarose column (commercially available from Qiagen) is prepared with abed volume of 5 mL, washed with 25 mL of water and equilibrated with 25mL of loading buffer. The filtered cell extract is loaded onto thecolumn at 0.5 mL per minute. The column is washed to baseline A₂₈₀ withloading buffer, at which point fraction collection is started. Next, thecolumn is washed with a secondary wash buffer (50 mM phosphate; 300 mMNaCl, 10% glycerol, pH 6.0), which elutes nonspecifically bound protein.After reaching A₂₈₀ baseline again, the column is developed with a 0 to500 mM Imidazole gradient in the secondary wash buffer. One mL fractionsare collected and analyzed by SDS-PAGE and silver staining or Westernblot with Ni²⁺-NTA-conjugated to alkaline phosphatase (Qiagen).Fractions containing the eluted His₁₀-tagged PRO are pooled and dialyzedagainst loading buffer.

Alternatively, purification of the IgG tagged (or Fc tagged) PRO can beperformed using known chromatography techniques, including for instance,Protein A or protein G column chromatography.

Many of the PRO polypeptides disclosed herein were successfullyexpressed as described above.

Example 144 Preparation of Antibodies that Bind PRO

This example illustrates preparation of monoclonal antibodies which canspecifically bind PRO.

Techniques for producing the monoclonal antibodies are known in the artand are described, for instance, in Goding, supra. Immunogens that maybe employed include purified PRO, fusion proteins containing PRO, andcells expressing recombinant PRO on the cell surface. Selection of theimmunogen can be made by the skilled artisan without undueexperimentation.

Mice, such as Balb/c, are immunized with the PRO immunogen emulsified incomplete Freund's adjuvant and injected subcutaneously orintraperitoneally in an amount from 1–100 micrograms. Alternatively, theimmunogen is emulsified in MPL-TDM adjuvant (Ribi ImmunochemicalResearch, Hamilton, Mont.) and injected into the animal's hind footpads. The immunized mice are then boosted 10 to 12 days later withadditional immunogen emulsified in the selected adjuvant. Thereafter,for several weeks, the mice may also be boosted with additionalimmunization injections. Serum samples may be periodically obtained fromthe mice by retro-orbital bleeding for testing in ELISA assays to detectanti-PRO antibodies.

After a suitable antibody titer has been detected, the animals“positive” for antibodies can be injected with a final intravenousinjection of PRO. Three to four days later, the mice are sacrificed andthe spleen cells are harvested. The spleen cells are then fused (using35% polyethylene glycol) to a selected murine myeloma cell line such asP3X63AgU.1, available from ATCC, No. CRL 1597. The fusions generatehybridoma cells which can then be plated in 96 well tissue cultureplates containing HAT (hypoxanthine, aminopterin, and thymidine) mediumto inhibit proliferation of non-fused cells, myeloma hybrids, and spleencell hybrids.

The hybridoma cells will be screened in an ELISA for reactivity againstPRO. Determination of “positive” hybridoma cells secreting the desiredmonoclonal antibodies against PRO is within the skill in the art.

The positive hybridoma cells can be injected intraperitoneally intosyngeneic Balb/c mice to produce ascites containing the anti-PROmonoclonal antibodies. Alternatively, the hybridoma cells can be grownin tissue culture flasks or roller bottles. Purification of themonoclonal antibodies produced in the ascites can be accomplished usingammonium sulfate precipitation, followed by gel exclusionchromatography. Alternatively, affinity chromatography based uponbinding of antibody to protein A or protein G can be employed.

Example 145 Purification of PRO Polypeptides Using Specific Antibodies

Native or recombinant PRO polypeptides may be purified by a variety ofstandard techniques in the art of protein purification. For example,pro-PRO polypeptide, mature PRO polypeptide, or pre-PRO polypeptide ispurified by immunoaffinity chromatography using antibodies specific forthe PRO polypeptide of interest. In general, an immunoaffinity column isconstructed by covalently coupling the anti-PRO polypeptide antibody toan activated chromatographic resin.

Polyclonal immunoglobulins are prepared from immune sera either byprecipitation with ammonium sulfate or by purification on immobilizedProtein A (Pharmacia LKB Biotechnology, Piscataway, N.J.). Likewise,monoclonal antibodies are prepared from mouse ascites fluid by ammoniumsulfate precipitation or chromatography on immobilized Protein A.Partially purified immunoglobulin is covalently attached to achromatographic resin such as CnBr-activated SEPHAROSEM (Pharmacia LKBBiotechnology). The antibody is coupled to the resin, the resin isblocked, and the derivative resin is washed according to themanufacturer's instructions.

Such an immunoaffinity column is utilized in the purification of PROpolypeptide by preparing a fraction from cells containing PROpolypeptide in a soluble form. This preparation is derived bysolubilization of the whole cell or of a subcellular fraction obtainedvia differential centrifugation by the addition of detergent or by othermethods well known in the art. Alternatively, soluble PRO polypeptidecontaining a signal sequence may be secreted in useful quantity into themedium in which the cells are grown.

A soluble PRO polypeptide-containing preparation is passed over theimmunoaffinity column, and the column is washed under conditions thatallow the preferential absorbance of PRO polypeptide (e.g., high ionicstrength buffers in the presence of detergent). Then, the column iseluted under conditions that disrupt antibody/PRO polypeptide binding(e.g., a low pH buffer such as approximately pH 2–3, or a highconcentration of a chaotrope such as urea or thiocyanate ion), and PROpolypeptide is collected.

Example 146 Drug Screening

This invention is particularly useful for screening compounds by usingPRO polypeptides or binding fragment thereof in any of a variety of drugscreening techniques. The PRO polypeptide or fragment employed in such atest may either be free in solution, affixed to a solid support, borneon a cell surface, or located intracellularly. One method of drugscreening utilizes eukaryotic or prokaryotic host cells which are stablytransformed with recombinant nucleic acids expressing the PROpolypeptide or fragment. Drugs are screened against such transformedcells in competitive binding assays. Such cells, either in viable orfixed form, can be used for standard binding assays. One may measure,for example, the formation of complexes between PRO polypeptide or afragment and the agent being tested. Alternatively, one can examine thediminution in complex formation between the PRO polypeptide and itstarget cell or target receptors caused by the agent being tested.

Thus, the present invention provides methods of screening for drugs orany other agents which can affect a PRO polypeptide-associated diseaseor disorder. These methods comprise contacting such an agent with an PROpolypeptide or fragment thereof and assaying (I) for the presence of acomplex between the agent and the PRO polypeptide or fragment, or (ii)for the presence of a complex between the PRO polypeptide or fragmentand the cell, by methods well known in the art. In such competitivebinding assays, the PRO polypeptide or fragment is typically labeled.After suitable incubation, free PRO polypeptide or fragment is separatedfrom that present in bound form, and the amount of free or uncomplexedlabel is a measure of the ability of the particular agent to bind to PROpolypeptide or to interfere with the PRO polypeptide/cell complex.

Another technique for drug screening provides high throughput screeningfor compounds having suitable binding affinity to a polypeptide and isdescribed in detail in WO 84/03564, published on Sep. 13, 1984. Brieflystated, large numbers of different small peptide test compounds aresynthesized on a solid substrate, such as plastic pins or some othersurface. As applied to a PRO polypeptide, the peptide test compounds arereacted with PRO polypeptide and washed. Bound PRO polypeptide isdetected by methods well known in the art. Purified PRO polypeptide canalso be coated directly onto plates for use in the aforementioned drugscreening techniques. In addition, non-neutralizing antibodies can beused to capture the peptide and immobilize it on the solid support.

This invention also contemplates the use of competitive drug screeningassays in which neutralizing antibodies capable of binding PROpolypeptide specifically compete with a test compound for binding to PROpolypeptide or fragments thereof. In this manner, the antibodies can beused to detect the presence of any peptide which shares one or moreantigenic determinants with PRO polypeptide.

Example 147 Rational Drug Design

The goal of rational drug design is to produce structural analogs ofbiologically active polypeptide of interest (i.e., a PRO polypeptide) orof small molecules with which they interact, e.g., agonists,antagonists, or inhibitors. Any of these examples can be used to fashiondrugs which are more active or stable forms of the PRO polypeptide orwhich enhance or interfere with the function of the PRO polypeptide invivo (cf., Hodgson, Bio/Technology, 9: 19–21 (1991)).

In one approach, the three-dimensional structure of the PRO polypeptide,or of an PRO polypeptide-inhibitor complex, is determined by x-raycrystallography, by computer modeling or, most typically, by acombination of the two approaches. Both the shape and charges of the PROpolypeptide must be ascertained to elucidate the structure and todetermine active site(s) of the molecule. Less often, useful informationregarding the structure of the PRO polypeptide may be gained by modelingbased on the structure of homologous proteins. In both cases, relevantstructural information is used to design analogous PRO polypeptide-likemolecules or to identify efficient inhibitors. Useful examples ofrational drug design may include molecules which have improved activityor stability as shown by Braxton and Wells, Biochemistry 31:7796–7801(1992) or which act as inhibitors, agonists, or antagonists of nativepeptides as shown by Athauda et al., J. Biochem., 113:742–746 (1993).

It is also possible to isolate a target-specific antibody, selected byfunctional assay, as described above, and then to solve its crystalstructure. This approach, in principle, yields a pharmacore upon whichsubsequent drug design can be based. It is possible to bypass proteincrystallography altogether by generating anti-idiotypic antibodies(anti-ids) to a functional, pharmacologically active antibody. As amirror image of a mirror image, the binding site of the anti-ids wouldbe expected to be an analog of the original receptor. The anti-id couldthen be used to identify and isolate peptides from banks of chemicallyor biologically produced peptides. The isolated peptides would then actas the pharmacore.

By virtue of the present invention, sufficient amounts of the PROpolypeptide may be made available to perform such analytical studies asX-ray crystallography. In addition, knowledge of the PRO polypeptideamino acid sequence provided herein will provide guidance to thoseemploying computer modeling techniques in place of or in addition tox-ray crystallography.

Example 148 Stimulation of Heart Neonatal Hypertrophy (Assay 1)

This assay is designed to measure the ability of PRO polypeptides tostimulate hypertrophy of neonatal heart. PRO polypeptides testingpositive in this assay are expected to be useful for the therapeutictreatment of various cardiac insufficiency disorders.

Cardiac myocytes from 1-day old Harlan Sprague Dawley rats wereobtained. Cells (180 μl at 7.5×10⁴/ml, serum<0.1%, freshly isolated) areadded on day 1 to 96-well plates previously coated with DMEM/F12+4% FCS.Test samples containing the test PRO polypeptide or growth medium only(hegative control) (20 μl/well) are added directly to the wells onday 1. PGF (20 μl/well) is then added on day 2 at final concentration of10⁻⁶ M. The cells are then stained on day 4 and visually scored on day5, wherein cells showing no increase in size as compared to negativecontrols are scored 0.0, cells showing a small to moderate increase insize as compared to negative controls are scored 1.0 and cells showing alarge increase in size as compared to negative controls are scored 2.0.A positive result in the assay is a score of 1.0 or greater.

The following polypeptides tested positive in this assay: PRO1312.

Example 149 Stimulation of Endothelial Cell Proliferation (Assay 8)

This assay is designed to determine whether PRO polypeptides of thepresent invention show the ability to stimulate adrenal corticalcapillary endothelial cell (ACE) growth. PRO polypeptides testingpositive in this assay would be expected to be useful for thetherapeutic treatment of conditions or disorders where angiogenesiswould be beneficial including, for example, wound healing, and the like(as would agonists of these PRO polypeptides). Antagonists of the PROpolypeptides testing positive in this assay would be expected to beuseful for the therapeutic treatment of cancerous tumors.

Bovine adrenal cortical capillary endothelial (ACE) cells (from primaryculture, maximum of 12–14 passages) were plated in 96-well plates at 500cells/well per 100 microliter. Assay media included low glucose DMEM,10% calf serum, 2 mM glutamine, and 1×penicillin/streptomycin/fungizone. Control wells included the following:(1) no ACE cells added; (2) ACE cells alone; (3) ACE cells plus VEGF (5ng/ml); and (4) ACE cells plus FGF (5ng/ml). The control or test sample,(in 100 microliter volumes), was then added to the wells (at dilutionsof 1%, 0.1% and 0.01%, respectively). The cell cultures were incubatedfor 6–7 days at 37° C./5% CO₂. After the incubation, the media in thewells was aspirated, and the cells were washed 1× with PBS. An acidphosphatase reaction mixture (100 microliter; 0.1M sodium acetate, pH5.5, 0.1% Triton X-100, 10 mM p-nitrophenyl phosphate) was then added toeach well. After a 2 hour incubation at 37° C., the reaction was stoppedby addition of 10 microliters 1N NaOH. Optical density (OD) was measuredon a microplate reader at 405 nm.

The activity of a PRO polypeptide was calculated as the fold increase inproliferation (as determined by the acid phosphatase activity, OD 405nm) relative to (1) cell only background, and (2) relative to maximumstimulation by VEGF. VEGF (at 3–10 ng/ml) and FGF (at 1–5 ng/ml) wereemployed as an activity reference for maximum stimulation. Results ofthe assay were considered “positive” if the observed stimulation was≦50%increase over background. VEGF (5 ng/ml) control at 1% dilution gave1.24 fold stimulation; FGF (5 ng/ml) control at 1% dilution gave 1.46fold stimulation.

The following PRO polypeptides tested positive in this assay: PRO1154and PRO1186.

Example 150 Inhibition of Vascular Endothelial Growth Factor (VEGF)Stimulated Proliferation of Endothelial Cell Growth (Assay 9)

The ability of various PRO polypeptides to inhibit VEGF stimulatedproliferation of endothelial cells was tested. Polypeptides testingpositive in this assay are useful for inhibiting endothelial cell growthin mammals where such an effect would be beneficial, e.g., forinhibiting tumor growth.

Specifically, bovine adrenal cortical capillary endothelial cells (ACE)(from primary culture, maximum of 12–14 passages) were plated in 96-wellplates at 500 cells/well per 100 microliter. Assay media included lowglucose DMEM, 10% calf serum, 2 mM glutamine, and 1×penicillin/streptomycin/fungizone. Control wells included the following:(1) no ACE cells added; (2) ACE cells alone; (3) ACE cells plus 5 ng/mlFGF; (4) ACE cells plus 3 ng/ml VEGF; (5) ACE cells plus 3 ng/ml VEGFplus 1 ng/ml TGF-beta; and (6) ACE cells plus 3 ng/ml VEGF plus 5 ng/mlLIF. The test samples, poly-his tagged PRO polypeptides (in 100microliter volumes), were then added to the wells (at dilutions of 1%,0.1% and 0.01%, respectively). The cell cultures were incubated for 6–7days at 37° C./5% CO₂. After the incubation, the media in the wells wasaspirated, and the cells were washed 1× with PBS. An acid phosphatasereaction mixture (100 microliter; 0.1M sodium acetate, pH 5.5, 0.1%Triton X-100, 10 mM p-nitrophenylphosphate) was then added to each well.After a 2 hour incubation at 37° C., the reaction was stopped byaddition of 10 microliters 1N NaOH. Optical density (OD) was measured ona microplate reader at 405 nm.

The activity of PRO polypeptides was calculated as the percentinhibition of VEGF (3 ng/ml) stimulated proliferation (as determined bymeasuring acid phosphatase activity at OD 405 nm) relative to the cellswithout stimulation. TGF-beta was employed as an activity reference at 1ng/ml, since TGF-beta blocks 70–90% of VEGF-stimulated ACE cellproliferation. The results are indicative of the utility of the PROpolypeptides in cancer therapy and specifically in inhibiting tumorangiogenesis. Numerical values (relative inhibition) are determined bycalculating the percent inhibition of VEGF stimulated proliferation bythe PRO polypeptides relative to cells without stimulation and thendividing that percentage into the percent inhibition obtained by TGF-βat 1 ng/ml which is known to block 70–90% of VEGF stimulated cellproliferation. The results are considered positive if the PROpolypeptide exhibits 30% or greater inhibition of VEGF stimulation ofendothelial cell growth (relative inhibition 30% or greater).

The following polypeptide tested positive in this assay: PRO812.

Example 151 Stimulatory Activity in Mixed Lymphocyte Reaction (MLR)Assay (Assay 24)

This example shows that certain polypeptides of the invention are activeas a stimulator of the proliferation of stimulated T-lymphocytes.Compounds which stimulate proliferation of lymphocytes are usefultherapeutically where enhancement of an immune response is beneficial. Atherapeutic agent may take the form of antagonists of the polypeptide ofthe invention, for example, murine-human chimeric, humanized or humanantibodies against the polypeptide.

The basic protocol for this assay is described in Current Protocols inImmunology, unit 3.12; edited by J E Coligan, A M Kruisbeek, D HMarglies, E M Shevach, W Strober, National Insitutes of Health,Published by John Wiley & Sons, Inc.

More specifically, in one assay variant, peripheral blood mononuclearcells (PBMC) are isolated from mammalian individuals, for example ahuman volunteer, by leukopheresis (one donor will supply stimulatorPBMCs, the other donor will supply responder PBMCs). If desired, thecells are frozen in fetal bovine serum and DMSO after isolation. Frozencells may be thawed overnight in assay media (37° C., 5% CO₂) and thenwashed and resuspended to 3×10⁶ cells/ml of assay media (RPMI; 10% fetalbovine serum, 1% penicillin/streptomycin, 1% glutamine, 1% HEPES, 1%non-essential amino acids, 1% pyruvate). The stimulator PBMCs areprepared by irradiating the cells (about 3000 Rads).

The assay is prepared by plating in triplicate wells a mixture of:

100:1 of test sample diluted to 1% or to 0.1%,

50:1 of irradiated stimulator cells, and

50:1 of responder PBMC cells.

100 microliters of cell culture media or 100 microliter of CD4-IgG isused as the control. The wells are then incubated at 37° C., 5% CO₂ for4 days. On day 5, each well is pulsed with tritiated thymidine (1.0mC/well; Amersham). After 6 hours the cells are washed 3 times and thenthe uptake of the label is evaluated.

In another variant of this assay, PBMCs are isolated from the spleens ofBalb/c mice and C57B6 mice. The cells are teased from freshly harvestedspleens in assay media (RPMI; 10% fetal bovine serum, 1%penicillin/streptomycin, 1% glutamine, 1% HEPES, 1% non-essential aminoacids, 1% pyruvate) and the PBMCs are isolated by overlaying these cellsover Lympholyte M (Organon Teknika), centrifuging at 2000 rpm for 20minutes, collecting and washing the mononuclear cell layer in assaymedia and resuspending the cells to 1×10⁷ cells/ml of assay media. Theassay is then conducted as described above.

Positive increases over control are considered positive with increasesof greater than or equal to 180% being preferred. However, any valuegreater than control indicates a stimulatory effect for the testprotein.

The following PRO polypeptides tested positive in this assay: PRO826,PRO1068, PRO1184, PRO1346 and PRO1375.

Example 152 Retinal Neuron Survival (Assay 52)

This example demonstrates that certain PRO polypeptides have efficacy inenhancing the survival of retinal neuron cells and, therefore, areuseful for the therapeutic treatment of retinal disorders or injuriesincluding, for example, treating sight loss in mammals due to retinitispigmentosum, AMD, etc.

Sprague Dawley rat pups at postnatal day 7 (mixed population: glia andretinal neuronal types) are killed by decapitation following CO₂anesthesia and the eyes are removed under sterile conditions. The neuralretina is dissected away from the pigment epithelium and other oculartissue and then dissociated into a single cell suspension using 0.25%trypsin in Ca²⁺, Mg²⁺-free PBS. The retinas are incubated at 37° C. for7–10 minutes after which the trypsin is inactivated by adding 1 mlsoybean trypsin inhibitor. The cells are plated at 100,000 cells perwell in 96 well plates in DMEM/F12 supplemented with N2 and with orwithout the specific test PRO polypeptide. Cells for all experiments aregrown at 37° C. in a water saturated atmosphere of 5% CO₂. After 2–3days in culture, cells are stained with calcein AM then fixed using 4%paraformaldehyde and stained with DAPI for determination of total cellcount. The total cells (fluorescent) are quantified at 20× objectivemagnification using CCD camera and NIH image software for Macintosh.Fields in the well are chosen at random.

The effect of various concentration of PRO polypeptides are reportedherein where percent survival is calculated by dividing the total numberof calcein AM positive cells at 2–3 days in culture by the total numberof DAPI-labeled cells at 2–3 days in culture. Anything above 30%survival is considered positive.

The following PRO polypeptides tested positive in this assay usingpolypeptide concentrations within the range of 0.01% to 1.0% in theassay: PRO828, PRO826, PRO1068 and PRO1132.

Example 153 Rod Photoreceptor Cell Survival (Assay 56)

This assay shows that certain polypeptides of the invention act toenhance the survival/proliferation of rod photoreceptor cells and,therefore, are useful for the therapeutic treatment of retinal disordersor injuries including, for example, treating sight loss in mammals dueto retinitis pigmentosum, AMD, etc.

Sprague Dawley rat pups at 7 day postnatal (mixed population: glia andretinal neuronal cell types) are killed by decapitation following CO₂anesthesis and the eyes are removed under sterile conditions. The neuralretina is dissected away form the pigment epithelium and other oculartissue and then dissociated into a single cell suspension using 0.25%trypsin in Ca²⁺, Mg²⁺-free PBS. The retinas are incubated at 37° C. for7–10 minutes after which the trypsin is inactivated by adding 1 mlsoybean trypsin inhibitor. The cells are plated at 100,000 cells perwell in 96 well plates in DMEM/F12 supplemented with N₂. Cells for allexperiments are grown at 37° C. in a water saturated atmosphere of 5%CO₂. After 2–3 days in culture, cells are fixed using 4%paraformaldehyde, and then stained using CellTracker Green CMFDA. Rho4D2 (ascites or IgG 1:100), a monoclonal antibody directed towards thevisual pigment rhodopsin is used to detect rod photoreceptor cells byindirect immunofluorescence. The results are calculated as % survival:total number of calcein-rhodopsin positive cells at 2–3 days in culture,divided by the total number of rhodopsin positive cells at time 2–3 daysin culture. The total cells (fluorescent) are quantified at 20×objective magnification using a CCD camera and NIH image software forMacIntosh. Fields in the well are chosen at random.

The following polypeptides tested positive in this assay: PRO536,PRO943, PRO828, PRO826, PRO1068 and PRO1132.

Example 154 Induction of c-fos in Endothelial Cells (Assay 34)

This assay is designed to determine whether PRO polypeptides show theability to induce c-fos in endothelial cells. PRO polypeptides testingpositive in this assay would be expected to be useful for thetherapeutic treatment of conditions or disorders where angiogenesiswould be beneficial including, for example, wound healing, and the like(as would agonists of these PRO polypeptides). Antagonists of the PROpolypeptides testing positive in this assay would be expected to beuseful for the therapeutic treatment of cancerous tumors.

Human venous umbilical vein endothelial cells (HUVEC, Cell Systems) ingrowth media (50% Ham's F12 w/o GHT: low glucose, and 50% DMEM withoutglycine: with NaHCO3, 1% glutamine, 10 mM HEPES, 10% FBS, 10 ng/ml bFGF)were plated on 96-well microtiter plates at a cell density of 1×10⁴cells/well. The day after plating, the cells were starved by removingthe growth media and treating the cells with 100 μl/well test samplesand controls (positive control=growth media; negative control=Protein 32buffer=10 mM HEPES, 140 mM NaCl, 4% (w/v) mannitol, pH 6.8). The cellswere incubated for 30 minutes at 37° C., in 5% CO₂. The samples wereremoved, and the first part of the bDNA kit protocol (ChironDiagnostics, cat. #6005–037) was followed, where each capitalizedreagent/buffer listed below was available from the kit.

Briefly, the amounts of the TM Lysis Buffer and Probes needed for thetests were calculated based on information provided by the manufacturer.The appropriate amounts of thawed Probes were added to the TM LysisBuffer. The Capture Hybridization Buffer was warmed to room temperature.The bDNA strips were set up in the metal strip holders, and 100 μl ofCapture Hybridization Buffer was added to each b-DNA well needed,followed by incubation for at least 30 minutes. The test plates with thecells were removed from the incubator, and the media was gently removedusing the vacuum manifold. 100 μl of Lysis Hybridization Buffer withProbes were quickly pipetted into each well of the microtiter plates.The plates were then incubated at 55° C. for 15 minutes. Upon removalfrom the incubator, the plates were placed on the vortex mixer with themicrotiter adapter head and vortexed on the #2 setting for one minute.80 μl of the lysate was removed and added to the bDNA wells containingthe Capture Hybridization Buffer, and pipetted up and down to mix. Theplates were incubated at 53° C. for at least 16 hours.

On the next day, the second part of the bDNA kit protocol was followed.Specifically, the plates were removed from the incubator and placed onthe bench to cool for 10 minutes. The volumes of additions needed werecalculated based upon information provided by the manufacturer. AnAmplifier Working Solution was prepared by making a 1:100 dilution ofthe Amplifier Concentrate (20 fm/μl) in AL Hybridization Buffer. Thehybridization mixture was removed from the plates and washed twice withWash A. 50 μl of Amplifier Working Solution was added to each well andthe wells were incubated at 53° C. for 30 minutes. The plates were thenremoved from the incubator and allowed to cool for 10 minutes. The LabelProbe Working Solution was prepared by making a 1:100 dilution of LabelConcentrate (40 pmoles/μl) in AL Hybridization Buffer. After the10-minute cool-down period, the amplifier hybridization mixture wasremoved and the plates were washed twice with Wash A. 50 μl of LabelProbe Working Solution was added to each well and the wells wereincubated at 53° C. for 15 minutes. After cooling for 10 minutes, theSubstrate was warmed to room temperature. Upon addition of 3 μl ofSubstrate Enhancer to each ml of Substrate needed for the assay, theplates were allowed to cool for 10 minutes, the label hybridizationmixture was removed, and the plates were washed twice with Wash A andthree times with Wash D. 50 μl of the Substrate Solution with Enhancerwas added to each well. The plates were incubated for 30 minutes at 37°C. and RLU was read in an appropriate luminometer.

The replicates were averaged and the coefficient of variation wasdetermined. The measure of activity of the fold increase over thenegative control (Protein 32/HEPES buffer described above) value wasindicated by chemiluminescence units (RLU). The results are consideredpositive if the PRO polypeptide exhibits at least a two-fold value overthe negative buffer control. Negative control=1.00 RLU at 1.00%dilution. Positive control=8.39 RLU at 1.00% dilution.

The following PRO polypeptides tested positive in this assay: PRO535,PRO826, PRO819, PRO1126, PRO1160 and PRO1387.

Example 155 Inhibitory Activity in Mixed Lymphocyte Reaction (MLR) Assay(Assay 67)

This example shows that one or more of the polypeptides of the inventionare active as inhibitors of the proliferation of stimulatedT-lymphocytes. Compounds which inhibit proliferation of lymphocytes areuseful therapeutically where suppression of an immune response isbeneficial.

The basic protocol for this assay is described in Current Protocols inImmunology, unit 3.12; edited by J E Coligan, A M Kruisbeek, D HMarglies, E M Shevach, W Strober, National Insitutes of Health,Published by John Wiley & Sons, Inc.

More specifically, in one assay variant, peripheral blood mononuclearcells (PBMC) are isolated from mammalian individuals, for example ahuman volunteer, by leukopheresis (one donor will supply stimulatorPBMCs, the other donor will supply responder PBMCs). If desired, thecells are frozen in fetal bovine serum and DMSO after isolation. Frozencells may be thawed overnight in assay media (37° C., 5% CO₂) and thenwashed and resuspended to 3×10⁶ cells/ml of assay media (RPMI; 10% fetalbovine serum, 1% penicillin/streptomycin, 1% glutamine, 1% HEPES, 1%non-essential amino acids, 1% pyruvate). The stimulator PBMCs areprepared by irradiating the cells (about 3000 Rads).

The assay is prepared by plating in triplicate wells a mixture of:

100:1 of test sample diluted to 1% or to 0.1%,

50 :1 of irradiated stimulator cells, and

50 :1 of responder PBMC cells.

100 microliters of cell culture media or 100 microliter of CD4-IgG isused as the control. The wells are then incubated at 37° C., 5% CO₂ for4 days. On day 5, each well is pulsed with tritiated thymidine (1.0mC/well; Amersham). After 6 hours the cells are washed 3 times and thenthe uptake of the label is evaluated.

In another variant of this assay, PBMCs are isolated from the spleens ofBalb/c mice and C57B6 mice. The cells are teased from freshly harvestedspleens in assay media (RPMI; 10% fetal bovine serum, 1%penicillin/streptomycin, 1% glutamine, 1% HEPES, 1% non-essential aminoacids, 1% pyruvate) and the PBMCs are isolated by overlaying these cellsover Lympholyte M (Organon Teknika), centrifuging at 2000 rpm for 20minutes, collecting and washing the mononuclear cell layer in assaymedia and resuspending the cells to 1×10⁷ cells/ml of assay media. Theassay is then conducted as described above.

Any decreases below control is considered to be a positive result for aninhibitory compound, with decreases of less than or equal to 80% beingpreferred. However, any value less than control indicates an inhibitoryeffect for the test protein.

The following polypeptide tested positive in this assay: PRO1114,PRO836, PRO1159, PRO1312, PRO1192, PRO1195 and PRO1387.

Example 156 Mouse Kidney Mesangial Cell Proliferation Assay (Assay 92)

This assay shows that certain polypeptides of the invention act toinduce proliferation of mammalian kidney mesangial cells and, therefore,are useful for treating kidney disorders associated with decreasedmesangial cell function such as Berger disease or other nephropathiesassociated with Schönlein-Henoch purpura, celiac disease, dermatitisherpetiformis or Crohn disease. The assay is performed as follows. Onday one, mouse kidney mesangial cells are plated on a 96 well plate ingrowth media (3:1 mixture of Dulbecco's modified Eagle's medium andHam's F12 medium, 95% fetal bovine serum, 5% supplemented with 14 mMHEPES) and grown overnight. On day 2, PRO polypeptides are diluted at 2concentrations(1% and 0.1%) in serum-free medium and added to the cells.Control samples are serum-free medium alone. On day 4, 20 μl of the CellTiter 96 Aqueous one solution reagent (Progema) was added to each welland the colormetric reaction was allowed to proceed for 2 hours. Theabsorbance (OD) is then measured at 490 nm. A positive in the assay isanything that gives an absorbance reading which is at least 15% abovethe control reading.

The following polypeptide tested positive in this assay: PRO819, PRO813and PRO1066.

Example 157 Pericyte c-Fos Induction (Assay 93)

This assay shows that certain polypeptides of the invention act toinduce the expression of c-fos in pericyte cells and, therefore, areuseful not only as diagnostic markers for particular types ofpericyte-associated tumors but also for giving rise to antagonists whichwould be expected to be useful for the therapeutic treatment ofpericyte-associated tumors. Specifically, on day 1, pericytes arereceived from VEC Technologies and all but 5 ml of media is removed fromflask. On day 2, the pericytes are trypsinized, washed, spun and thenplated onto 96 well plates. On day 7, the media is removed and thepericytes are treated with 100 μl of PRO polypeptide test samples andcontrols (positive control=DME+5% serum +/−PDGF at 500 ng/ml; negativecontrol=protein 32). Replicates are averaged and SD/CV are determined.Fold increase over Protein 32 (buffer control) value indicated bychemilumninescence units (RLU) luminometer reading verses frequency isplotted on a histogram. Two-fold above Protein 32 value is consideredpositive for the assay. ASY Matrix: Growth media=low glucose DMEM=20%FBS+1× pen strep+1× fingizone. Assay Media=low glucose DMEM+5% FBS.

The following polypeptides tested positive in this assay: PRO943 andPRO819.

Example 158 Detection of PRO Polypeptides that Affect Glucose or FFAUptake by Primary Rat Adipocytes (Assay 94)

This assay is designed to determine whether PRO polypeptides show theability to affect glucose or FFA uptake by adipocyte cells. PROpolypeptides testing positive in this assay would be expected to beuseful for the therapeutic treatment of disorders where either thestimulation or inhibition of glucose uptake by adipocytes would bebeneficial including, for example, obesity, diabetes or hyper- orhypo-insulinemia.

In a 96 well format, PRO polypeptides to be assayed are added to primaryrat adipocytes, and allowed to incubate overnight. Samples are taken at4 and 16 hours and assayed for glycerol, glucose and FFA uptake. Afterthe 16 hour incubation, insulin is added to the media and allowed toincubate for 4 hours. At this time, a sample is taken and glycerol,glucose and FFA uptake is measured. Media containing insulin without thePRO polypeptide is used as a positive reference control. As the PROpolypeptide being tested may either stimulate or inhibit glucose and FFAuptake, results are scored as positive in the assay if greater than 1.5times or less than 0.5 times the insulin control.

The following PRO polypeptides tested positive as stimulators of glucoseand/or FFA uptake in this assay: PRO1114, PRO1007, PRO1066, PRO848,PRO1182, PRO1198, PRO1192, PRO1271, PRO1375 and PRO1387.

The following PRO polypeptides tested positive as inhibitors of glucoseand/or FFA uptake in this assay: PRO1184, PRO1360, PRO1309, PRO1154,PRO1181, PRO1186, PRO1160 and PRO1384.

Example 159 Chondrocyte Re-differentiation Assay (Assay 110)

This assay shows that certain polypeptides of the invention act toinduce redifferentiation of chondrocytes, therefore, are expected to beuseful for the treatment of various bone and/or cartilage disorders suchas, for example, sports injuries and arthritis. The assay is performedas follows. Porcine chondrocytes are isolated by overnight collagenasedigestion of articulary cartilage of metacarpophalangeal joints of 4–6month old female pigs. The isolated cells are then seeded at 25,000cells/cm² in Ham F-12 containing 10% FBS and 4 μg/ml gentamycin. Theculture media is changed every third day and the cells are then seededin 96 well plates at 5,000 cells/well in 100μl of the same media withoutserum and 100 μl of the test PRO polypeptide, 5 nM staurosporin(positive control) or medium alone (negative control) is added to give afinal volume of 200 μl/well. After 5 days of incubation at 37° C., apicture of each well is taken and the differentiation state of thechondrocytes is determined. A positive result in the assay occurs whenthe redifferentiation of the chondrocytes is determined to be moresimilar to the positive control than the negative control.

The following polypeptide tested positive in this assay: PRO1282,PRO1310, PRO619, PRO943, PRO820, PRO1080, PRO1016, PRO1007, PRO1056,PRO791, PRO1111, PRO1184, PRO1360, PRO1309 PRO1107, PRO1132, PRO1131,PRO848, PRO1181, PRO1186, PRO1159, PRO1312, PRO1192 and PRO1384.

Example 160 Chondrocyte Proliferation Assay (Assay 111)

This assay is designed to determine whether PRO polypeptides of thepresent invention show the ability to induce the proliferation and/orredifferentiation of chondrocytes in culture. PRO polypeptides testingpositive in this assay would be expected to be useful for thetherapeutic treatment of various bone and/or cartilage disorders suchas, for example, sports injuries and arthritis.

Porcine chondrocytes are isolated by overnight collagenase digestion ofarticular cartilage of the metacarpophalangeal joint of 4–6 month oldfemale pigs. The isolated cells are then seeded at 25,000 cells/cm² inHam F-12 containing 10% FBS and 4 μg/ml gentamycin. The culture media ischanged every third day and the cells are reseeded to 25,000 cells/cm²every five days. On day 12, the cells are seeded in 96 well plates at5,000 cells/well in 100 μl of the same media without serum and 100 μl ofeither serum-free medium (negative control), staurosporin (finalconcentration of 5 nM; positive control) or the test PRO polypeptide areadded to give a final volume of 200 μl/well. After 5 days at 37° C., 20μl of Alamar blue is added to each well and the plates are incubated foran additional 3 hours at 37° C. The fluorescence is then measured ineach well (Ex:530 nm; Em: 590 nm). The fluorescence of a platecontaining 200 μl of the serum-free medium is measured to obtain thebackground. A positive result in the assay is obtained when thefluorescence of the PRO polypeptide treated sample is more like that ofthe positive control than the negative control.

The following PRO polypeptides tested positive in this assay: PRO1310,PRO844, PRO1312, PRO1192 and PRO1387.

Example 161 Induction of Pancreatic β-Cell Precursor Proliferation(Assay 117)

This assay shows that certain polypeptides of the invention act toinduce an increase in the number of pancreatic β-cell precursor cellsand, therefore, are useful for treating various insulin deficient statesin mammals, including diabetes mellitus. The assay is performed asfollows. The assay uses a primary culture of mouse fetal pancreaticcells and the primary readout is an alteration in the expression ofmarkers that represent either β-cell precursors or mature β-cells.Marker expression is measured by real time quantitative PCR (RTQ-PCR);wherein the marker being evaluated is a transcription factor calledPdx1.

The pancreata are dissected from E14 embryos (CD1 mice). The pancreataare then digested with collagenase/dispase in F12/DMEM at 37° C. for 40to 60 minutes (collagenase/dispase, 1.37 mg/ml, Boehringer Mannheim,#1097113). The digestion is then neutralized with an equal volume of 5%BSA and the cells are washed once with RPMI1640. At day 1, the cells areseeded into 12-well tissue culture plates (pre-coated with laminin,20μg/ml in PBS, Boehringer Mannheim, #124317). Cells from pancreata from1–2 embryos are distributed per well. The culture medium for thisprimary cuture is 14F/1640. At day 2, the media is removed and theattached cells washed with RPMI/1640. Two mls of minimal media are addedin addition to the protein to be tested. At day 4, the media is removedand RNA prepared from the cells and marker expression analyzed by realtime quantitative RT-PCR. A protein is considered to be active in theassay if it increases the expression of the relevant β-cell marker ascompared to untreated controls.

14F/1640 is RPMI1640 (Gibco) plus the following:

group A 1:1000

group B 1:1000

recombinant human insulin 10 μg/ml

Aprotinin (50 μg/ml) 1:2000 (Boehringer manheim #981532)

Bovine pituitary extract (BPE) 60 μg/ml

Gentamycin 100 ng/ml

Group A: (in 10 ml PBS)

Transferrin, 100 mg (Sigma T2252)

Epidermal Growth Factor, 100μg (BRL 100004)

Triiodothyronine, 10 μl of 5×10⁻⁶ M (Sigma T5516)

Ethanolamine, 100 μl of 10⁻¹ M (Sigma E0135)

Phosphoethalamine, 100μl of 10⁻¹ M (Sigma P0503)

Selenium, 4 μl of 10⁻¹ M (Aesar #12574)

Group C: (in 10 ml 100% ethanol)

Hydrocortisone, 2 μl of 5×10⁻³ M(Sigma #H0135)

Progesterone, 100 μl of 1×10⁻³ M (Sigma #P6149)

Forskolin, 500 μl of 20 mM (Calbiochem #344270)

Minimal media:

RPMI 1640 plus transferrin (10 μg/ml), insulin (1 μg/ml), gentamycin(100 ng/ml), aprotinin (50 μg/ml) and BPE (15 μg/ml).

Defined media:

RPMI 1640 plus transferrin (10 μg/ml), insulin (1 μg/ml), gentamycin(100 ng/ml) and aprotinin (50 μg/ml).

The following polypeptides tested positive in this assay: PRO1310,PRO1188, PRO1131 and PRO1387.

Example 162 Detection of Polypeptides that Affect Glucose or FFA Uptakein Skeletal Muscle (Assay 106)

This assay is designed to determine whether PRO polypeptides show theability to affect glucose or FFA uptake by skeletal muscle cells. PROpolypeptides testing positive in this assay would be expected to beuseful for the therapeutic treatment of disorders where either thestimulation or inhibition of glucose uptake by skeletal muscle would bebeneficial including, for example, diabetes or hyper- orhypo-insulinemia.

In a 96 well format, PRO polypeptides to be assayed are added to primaryrat differentiated skeletal muscle, and allowed to incubate overnight.Then fresh media with the PRO polypeptide and +/−insulin are added tothe wells. The sample media is then monitored to determine glucose andFFA uptake by the skeletal muscle cells. The insulin will stimulateglucose and FFA uptake by the skeletal muscle, and insulin in mediawithout the PRO polypeptide is used as a positive control, and a limitfor scoring. As the PRO polypeptide being tested may either stimulate orinhibit glucose and FFA uptake, results are scored as positive in theassay if greater than 1.5 times or less than 0.5 times the insulincontrol.

The following PRO polypeptides tested positive as either stimulators orinhibitors of glucose and/or FFA uptake in this assay: PRO358, PRO1016,PRO1007, PRO826, PRO1066, PRO1029 and PRO1309.

Example 163 Fetal Hemoglobin Induction in an Erythroblastic Cell Line(Assay 107)

This assay is useful for screening PRO polypeptides for the ability toinduce the switch from adult hemoglobin to fetal hemoglobin in anerythroblastic cell line. Molecules testing positive in this assay areexpected to be useful for therapeutically treating various mammalianhemoglobin-associated disorders such as the various thalassemias. Theassay is performed as follows. Erythroblastic cells are plated instandard growth medium at 1000 cells/well in a 96 well format. PROpolypeptides are added to the growth medium at a concentration of 0.2%or 2% and the cells are incubated for 5 days at 37° C. As a positivecontrol, cells are treated with 100 μM hemin and as a negative control,the cells are untreated. After 5 days, cell lysates are prepared andanalyzed for the expression of gamma globin (a fetal marker). A positivein the assay is a gamma globin level at least 2-fold above the negativecontrol.

The following polypeptides tested positive in this assay: PRO114,PRO826, PRO1066, PRO844, PRO1192 and PRO1358.

Example 164 Induction of Pancreatic β-Cell Precursor Differentiation(Assay 89)

This assay shows that certain polypeptides of the invention act toinduce differentiation of pancreatic β-cell precursor cells into maturepancreatic β-cells and, therefore, are useful for treating variousinsulin deficient states in mammals, including diabetes mellitus. Theassay is performed as follows. The assay uses a primary culture of mousefetal pancreatic cells and the primary readout is an alteration in theexpression of markers that represent either β-cell precursors or matureβ-cells. Marker expression is measured by real time quantitative PCR(RTQ-PCR); wherein the marker being evaluated is insulin.

The pancreata are dissected from E14 embryos (CD1 mice). The pancreataare then digested with collagenase/dispase in F12/DMEM at 37° C. for 40to 60 minutes (collagenase/dispase, 1.37 mg/ml, Boehringer Marnheim,#1097113). The digestion is then neutralized with an equal volume of 5%BSA and the cells are washed once with RPM11640. At day 1, the cells areseeded into 12-well tissue culture plates (pre-coated with laminin, 20μg/ml in PBS, Boehringer Mannheim, #124317). Cells from pancreata from1–2 embryos are distributed per well. The culture medium for thisprimary cuture is 14F/1640. At day 2, the media is removed and theattached cells washed with RPMI/1640. Two mls of minimal media are addedin addition to the protein to be tested. At day 4, the media is removedand RNA prepared from the cells and marker expression analyzed by realtime quantitative RT-PCR. A protein is considered to be active in theassay if it increases the expression of the relevant β-cell marker ascompared to untreated controls.

14F/1640 is RPMI1640 (Gibco) plus the following:

group A 1:1000

group B 1:1000

recombinant human insulin 10 μg/ml

Aprotinin (50 μg/ml) 1:2000 (Boehringer manheim #981532)

Bovine pituitary extract (BPE) 60 μg/ml

Gentamycin 100 ng/ml

Group A: (in 10 ml PBS)

Transferrin, 100 mg (Sigma T2252)

Epidermal Growth Factor, 100μg (BRL 100004)

Triiodothyronine, 10 μl of 5×10⁻⁶ M (Sigma T5516)

Ethanolamine, 100 μl of 10⁻¹ M (Sigma E0135)

Phosphoethalamine, 100 μl of 10⁻¹ M (Sigma P0503)

Selenium, 4 μl of 10⁻¹ M (Aesar #12574)

Group C : (in 10 ml 100% ethanol)

Hydrocortisone, 2 μl of 5×10⁻³ M (Sigma #H0135)

Progesterone, 100 μl of 1×10⁻³ M (Sigma #P6149)

Forskolin, 500 μl of 20 mM (Calbiochem #344270)

Minimal media:

RPMI 1640 plus transferrin (10 μg/ml), insulin (1 μg/ml), gentamycin(100 ng/ml), aprotinin (50 μg/ml) and BPE (15 μg/ml).

Defined media:

RPMI 1640 plus transferrin (10 μg/ml), insulin (1 μg/ml), gentamycin(100 ng/ml) and aprotinin (50 μg/ml).

The following polypeptides were positive in this assay: PRO1188,PRO1132, PRO1131 and PRO1181.

Example 165 Skin Vascular Permeability Assay (Assay 64)

This assay shows that certain polypeptides of the invention stimulate animmune response and induce inflammation by inducing mononuclear cell,eosinophil and PMN infiltration at the site of injection of the animal.Compounds which stimulate an immune response are useful therapeuticallywhere stimulation of an immune response is beneficial. This skinvascular permeability assay is conducted as follows. Hairless guineapigs weighing 350 grams or more are anesthetized with ketaniine (75–80mg/Kg) and 5 mg/Kg xylazine intramuscularly (IM). A sample of purifiedpolypeptide of the invention or a conditioned media test sample isinjected intradermally onto the backs of the test animals with 100 μlper injection site. It is possible to have about 10–30, preferably about16–24, injection sites per animal. One μl of Evans blue dye (1% inphysiologic buffered saline) is injected intracardially. Blemishes atthe injection sites are then measured (mm diameter) at 1 hr and 6 hrpost injection. Animals were sacrificed at 6 hrs after injection. Eachskin injection site is biopsied and fixed in formalin. The skins arethen prepared for histopathologic evaluation. Each site is evaluated forinflammatory cell infiltration into the skin. Sites with visibleinflammatory cell inflammation are scored as positive. Inflammatorycells may be neutrophilic, eosinophilic, monocytic or lymphocytic. Atleast a minimal perivascular infiltrate at the injection site is scoredas positive, no infiltrate at the site of injection is scored asnegative.

The following polypeptide tested positive in this assay: PRO1007,PRO1358 and PRO1375.

Example 166 Induction of Endothelial Cell Apoptosis (ELISA) (Assay 109)

The ability of PRO polypeptides to induce apoptosis in endothelial cellswas tested in human venous umbilical vein endothelial cells (HUVEC, CellSystems) using a 96-well format, in 0% serum media supplemented with 100ng/ml VEGF, 0.1% BSA, 1× penn/strep. A positive result in this assayindicates the usefulness of the polypeptide for therapeutically treatingany of a variety of conditions associated with undesired endothelialcell growth including, for example, the inhibition of tumor growth. The96-well plates used were manufactured by Falcon (No. 3072). Coating of96 well plates were prepared by allowing gelatinization to occur for >30minutes with 100 μl of 0.2% gelatin in PBS solution. The gelatin mix wasaspirated thoroughly before plating HUVEC cells at a final concentrationof 2×10⁴ cells/ml in 10% serum containing medium—100 μl volume per well.The cells were grown for 24 hours before adding test samples containingthe PRO polypeptide of interest.

To all wells, 100 μl of 0% serum media (Cell Systems) complemented with100 ng/ml VEGF, 0.1% BSA, 1× penn/strep was added. Test samplescontaining PRO polypeptides were added in triplicate at dilutions of 1%,0.33% and 0.11%. Wells without cells were used as a blank and wells withcells only were used as a negative control. As a positive control, 1:3serial dilutions of 50 μl of a 3× stock of staurosporine were used. Thecells were incubated for 24 to 35 hours prior to ELISA.

ELISA was used to determine levels of apoptosis preparing solutionsaccording to the Boehringer Manual [Boehringer, Cell Death DetectionELISA plus, Cat No. 1 920 685]. Sample preparations: 96 well plates werespun down at 1 krpm for 10 minutes (200 g); the supernatant was removedby fast inversion, placing the plate upside down on a paper towel toremove residual liquid. To each well, 200 μl of 1× Lysis buffer wasadded and incubation allowed at room temperature for 30 minutes withoutshaking. The plates were spun down for 10 minutes at 1 krpm, and 20 μlof the lysate (cytoplasmic fraction) was transferred into streptavidincoated MTP. 80 μl of immunoreagent mix was added to the 20 μl lystate ineach well. The MTP was covered with adhesive foil and incubated at roomtemperature for 2 hours by placing it on an orbital shaker (200 rpm).After two hours, the supernatant was removed by suction and the wellsrinsed three times with 250 μl of 1× incubation buffer per well (removedby suction). Substrate solution was added (100 μl) into each well andincubated on an orbital shaker at room temperature at 250 rpm untilcolor development was sufficient for a photometric analysis (approx.after 10–20 minutes). A 96 well reader was used to read the plates at405 nm, reference wavelength, 492 nm. The levels obtained for PIN 32(control buffer) was set to 100%. Samples with levels>130% wereconsidered positive for induction of apoptosis.

The following PRO polypeptides tested positive in this assay: PRO844.

Example 167 Guinea Pig Vascular Leak (Assay 32)

This assay is designed to determine whether PRO polypeptides of thepresent invention show the ability to induce vascular permeability.Polypeptides testing positive in this assay are expected to be usefulfor the therapeutic treatment of conditions which would benefit fromenhanced vascular permeability including, for example, conditions whichmay benefit from enhanced local immune system cell infiltration.

Hairless guinea pigs weighing 350 grams or more were anesthetized withKetamine (75–80 mg/kg) and 5 mg/kg Xylazine intramuscularly. Testsamples containing the PRO polypeptide or a physiological buffer withoutthe test polypeptide are injected into skin on the back of the testanimals with 100 μl per injection site intradermally. There wereapproximately 16–24 injection sites per animal. One ml of Evans blue dye(1% in PBS) is then injected intracardially. Skin vascular permeabilityresponses to the compounds (i.e., blemishes at the injection sites ofinjection) are visually scored by measuring the diameter (in mm) ofblue-colored leaks from the site of injection at 1, 6 and 24 hours postadministration of the test materials. The mm diameter of blueness at thesite of injection is observed and recorded as well as the severity ofthe vascular leakage. Blemishes of at least 5 mm in diameter areconsidered positive for the assay when testing purified proteins, beingindicative of the ability to induce vascular leakage or permeability. Aresponse greater than 7 mm diameter is considered positive forconditioned media samples. Human VEGF at 0.1 μg/100 μl is used as apositive control, inducing a response of 4–8 mm diameter.

The following PRO polypeptides tested positive in this assay:PRO1155.

Example 168 Mouse Mesengial Cell Inhibition Assay (Assay 114)

This assay is designed to determine whether PRO polypeptides of thepresent invention show the ability to inhibit the proliferation of mousemesengial cells in culture. PRO polypeptides testing positive in thisassay would be expected to be useful for the therapeutic treatment ofsuch diseases or conditions where inhibition of mesengial cellproliferation would be beneficial such as, for example, cystic renaldysplasia, polycystic kidney disease, or other kidney disease associatedwith abnormal mesengial cell proliferation, renal tumors, and the like.

On day 1, mouse mesengial cells are plated on a 96 well plate in growthmedium (a 3:1 mixture of Dulbecco's modified Eagle's medium and Ham'sF12 medium, 95%; fetal bovine serum, 5%; supplemented with 14 mM HEPES)and then are allowed to grow overnight. On day 2, the PRO polypeptide isdiluted at 2 different concentrations (1%, 0.1%) in serum-free mediumand is added to the cells. The negative control is growth medium withoutadded PRO polypeptide. After the cells are allowed to incubate for 48hours, 20 μl of the Cell Titer 96 Aqueous one solution reagent (Promega)is added to each well and the colormetric reaction is allowed to proceedfor 2 hours. The absorbance (OD) is then measured at 490 nm. A positivein the assay is an absorbance reading which is at least 10% above thenegative control.

The following PRO polypeptides tested positive in this assay: PRO1192and PRO1195.

Example 169 In Vitro Antitumor Assay (Assay 161)

The antiproliferative activity of various PRO polypeptides wasdetermined in the investigational, disease-oriented in vitro anti-cancerdrug discovery assay of the National Cancer Institute (NCI), using asulforhodamine B (SRB) dye binding assay essentially as described bySkehan et al., J. Natl. Cancer Inst. 82:1107–1112 (1990). The 60 tumorcell lines employed in this study (“the NCI panel”), as well asconditions for their maintenance and culture in vitro have beendescribed by Monks et al., J. Natl. Cancer Inst. 83:757–766 (1991). Thepurpose of this screen is to initially evaluate the cytotoxic and/orcytostatic activity of the test compounds against different types oftumors (Monks et al., supra; Boyd, Cancer: Princ. Pract. Oncol. Update3(10):1–12 [1989]).

Cells from approximately 60 human tumor cell lines were harvested withtrypsin/EDTA (Gibco), washed once, resuspended in IMEM and theirviability was determined. The cell suspensions were added by pipet (100μL volume) into separate 96-well microtiter plates. The cell density forthe 6-day incubation was less than for the 2-day incubation to preventovergrowth. Inoculates were allowed a preincubation period of 24 hoursat 37° C. for stabilization. Dilutions at twice the intended testconcentration were added at time zero in 100 μL aliquots to themicrotiter plate wells (1:2 dilution). Test compounds were evaluated atfive half-log dilutions (1000 to 100,000-fold). Incubations took placefor two days and six days in a 5% CO₂ atmosphere and 100% humidity.

After incubation, the medium was removed and the cells were fixed in 0.1ml of 10% trichloroacetic acid at 40° C. The plates were rinsed fivetimes with deionized water, dried, stained for 30 minutes with 0.1 ml of0.4% sulforhodamine B dye (Sigma) dissolved in 1% acetic acid, rinsedfour times with 1% acetic acid to remove unbound dye, dried, and thestain was extracted for five minutes with 0.1 ml of 10 mM Tris base[tris(hydroxymethyl)aminomethane], pH 10.5. The absorbance (OD) ofsulforhodamine B at 492 nm was measured using a computer-interfaced,96-well microtiter plate reader.

A test sample is considered positive if it shows at least 50% growthinhibitory effect at one or more concentrations. The results are shownin the following table, where the abbreviations are as follows:

-   NSCL=non-small cell lung carcinoma-   CNS=central nervous system

TABLE 7 Test Tumor Cell Cell Line compound Concentration Days Line TypeDesignation PRO1016 0.1 nM 2 Leukemia K-568 PRO1016 0.1 nM 2 LeukemiaMOLT-4 PRO1016 0.1 nM 2 Leukemia RPMI-8226 PRO1016 0.1 nM 2 NSCLA549/ATCC PRO1016 0.1 nM 2 NSCL EKVX PRO1016 0.1 nM 2 NSCL NCI-H23PRO1016 0.1 nM 2 NSCL NCI-H522 PRO1016 0.1 nM 2 Colon KM-12 PRO1016 0.1nM 2 CNS SF-295 PRO1016 0.1 nM 2 Melanoma SK-MEL-5 PRO1016 0.1 nM 2Melanoma UACC-257 PRO1016 0.1 nM 2 Ovarian OVCAR-3 PRO1016 0.1 nM 2Ovarian OVCAR-4 PRO1016 0.1 nM 2 Breast NCI/SDR-RES PRO1016 0.1 nM 2Breast T-47D PRO1016 0.1 nM 6 Leukemia CCRF-CEM PRO1016 0.1 nM 6Leukemia K-562 PRO1016 0.1 nM 6 Leukemia MOLT-4 PRO1016 0.1 nM 6Leukemia RPMI-8226 PRO1016 0.1 nM 6 NSCL A549/ATCC PRO1016 0.1 nM 6 NSCLEKVX PRO1016 0.1 nM 6 NSCL HOP-62 PRO1016 0.1 nM 6 NSCL NCI-H23 PRO10160.1 nM 6 NSCL NCI-H322M PRO1016 0.1 nM 6 NSCL NCI-H460 PRO1016 0.1 nM 6NSCL NCI-H522 PRO1016 0.1 nM 6 Colon COLO 205 PRO1016 0.1 nM 6 ColonCHT-116 PRO1016 0.1 nM 6 Colon HCT-15 PRO1016 0.1 nM 6 Colon HT-29PRO1016 0.1 nM 6 Colon SW-620 PRO1016 0.1 nM 6 CNS SF-295 PRO1016 0.1 nM6 CNS SF-539 PRO1016 0.1 nM 6 CNS SNB-19 PRO1016 0.1 nM 6 CNS U251PRO1016 0.1 nM 6 Melanoma LOX IMVI PRO1016 0.1 nM 6 Melanoma MALME-3MPRO1016 0.1 nM 6 Melanoma SK-MEL-28 PRO1016 0.1 nM 6 Melanoma SK-MEL-5PRO1016 0.1 nM 6 Melanoma UACC-257 PRO1016 0.1 nM 6 Melanoma UACC-62PRO1016 0.1 nM 6 Ovarian IGROV1 PRO1016 0.1 nM 6 Ovarian OVCAR-3 PRO10160.1 nM 6 Ovarian OVCAR-4 PRO1016 0.1 nM 6 Ovarian OVCAR-8 PRO1016 0.1 nM6 Renal ACHN PRO1016 0.1 nM 6 Renal RXF 393 PRO1016 0.1 nM 6 Renal SN12CPRO1016 0.1 nM 6 Renal TK-10 PRO1016 0.1 nM 6 Prostate PC-3 PRO1016 0.1nM 6 Breast MCF-7 PRO1016 0.1 nM 6 Breast NCI/ADR-RES PRO1016 0.1 nM 6Breast MDA-MB-231 PRO1016 0.1 nM 6 Breast MDA-MB-435 PRO1016 0.1 nM 6Breast MDA-N PRO1016 0.1 nM 6 Breast BT-549 PRO1016 0.1 nM 6 BreastT-47D PRO1186 95 nM 2 NSCL NCI-H226 PRO1186 95 nM 2 Colon Colo205PRO1186 2.2 nM 6 Breast MDA-N PRO1186 114 nM 2 NSCL NCI-H322M PRO1186114 nM 2 CNS SF-268; SF-539 PRO1186 114 nM 2 Ovarian IGFOV1 PRO1186 114nM 2 Renal 786-0; SN12C; TK-10 PRO1186 114 nM 6 Leukemia MOLT-4;RPMI-8226 PRO1186 114 nM 6 Melanoma LOX IMVI PRO1186 114 nM 6 OvarianOVCAR-4; SK-OV-3 PRO1186 114 nM 6 Breast MDA-MB-435; T-47D PRO1186 8.1nM 6 Leukemia K-562 PRO1186 8.1 nM 6 NSCL HOP-62 PRO1186 8.1 nM 6 ColonColo205; HCC-2998 PRO1186 8.1 nM 6 Breast T-47D PRO1186 15.4 nM 6Leukemia K-562 PRO1186 3.6 nM 2 Ovarian OVCAR-3 PRO1186 3.6 nM 6 NSCLHOP-62

The results of these assays demonstrate that the positive testing PROpolypeptides are useful for inhibiting neoplastic growth in a number ofdifferent tumor cell types and may be used therapeutically therefor.Antibodies against these PRO polypeptides are useful for affinitypurification of these useful polypeptides. Nucleic acids encoding thesePRO polypeptides are useful for the recombinant preparation of thesepolypeptides.

Example 170 Gene Amplification in Tumors

This example shows that certain PRO polypeptide-encoding genes areamplified in the genome of certain human lung, colon and/or breastcancers and/or cell lines. Amplification is associated withoverexpression of the gene product, indicating that the polypeptides areuseful targets for therapeutic intervention in certain cancers such ascolon, lung, breast and other cancers and diagnostic determination ofthe presence of those cancers. Therapeutic agents may take the form ofantagonists of the PRO polypeptide, for example, murine-human chimeric,humanized or human antibodies against a PRO polypeptide.

The starting material for the screen was genomic DNA isolated from avariety cancers. The DNA is quantitated precisely, e.g.,fluorometrically. As a negative control, DNA was isolated from the cellsof ten normal healthy individuals which was pooled and used as assaycontrols for the gene copy in healthy individuals (not shown). The 5′nuclease assay (for example, TaqMan™) and real-time quantitative PCR(for example, ABI Prizm 7700 Sequence Detection System™ (Perkin Elmer,Applied Biosystems Division, Foster City, Calif.)), were used to findgenes potentially amplified in certain cancers. The results were used todetermine whether the DNA encoding the PRO polypeptide isover-represented in any of the primary lung or colon cancers or cancercell lines or breast cancer cell lines that were screened. The primarylung cancers were obtained from individuals with tumors of the type andstage as indicated in Table 8. An explanation of the abbreviations usedfor the designation of the primary tumors listed in Table 8 and theprimary tumors and cell lines referred to throughout this example aregiven below.

The results of the TaqMan™ are reported in delta (Δ) Ct units. One unitcorresponds to 1 PCR cycle or approximately a 2-fold amplificationrelative to normal, two units corresponds to 4-fold, 3 units to 8-foldamplification and so on. Quantitation was obtained using primers and aTaqMan™ fluorescent probe derived from the PRO polypeptide-encodinggene. Regions of the PRO polypeptide-encoding gene which are most likelyto contain unique nucleic acid sequences and which are least likely tohave spliced out introns are preferred for the primer and probederivation, e.g., 3′-untranslated regions. The sequences for the primersand probes (forward, reverse and probe) used for the PRO polypeptidegene amplification analysis were as follows:

PRO290 (DNA35680-1212): 35680.tm.p: 5′-CCACCAATGGCAGCCCCACCT-3′ (SEQ IDNO:428) 35680.tm.f: 5′-GACTGCCCTCCCTGCCA-3′ (SEQ ID NO:429) 35680.tm.r:5′-CAAAAAGCCTGGAAGTCTTCAAAG-3′ (SEQ ID NO:430) PRO341 (DNA26288-1239):26288.tm.f1: 5′-CAGCTGGACTGCAGGTGCTA-3′ (SEQ ID NO:431) 26288.tm.r1:5′-CAGTGAGCACAGCAAGTGTCCT-3′ (SEQ ID NO:432) 26288.tm.p1:5′-GGCCACCTCCTTGAGTCTTCAGTTCCCT-3′ (SEQ ID NO:433) PRO535(DNA49143-1429): 49143.tm.f1: 5′-CAACTACTGGCTAAAGCTGGTGAA-3′ (SEQ IDNO:434) 49143.tm.r1: 5′-CCTTTCTGTATAGGTGATACCCAATGA-3′ (SEQ ID NO:435)49143.tm.p1: 5′-TGGCCATCCCTACCAGAGGCAAAA-3′ (SEQ ID NO:436) PRO619(DNA49821-1562): 49821.tm.f1: 5′-CTGAAGACGACGCGGATTACTA-3′ (SEQ IDNO:437) 49821.tm.r1: 5′-GGCAGAAATGGGAGGCAGA-3′ (SEQ ID NO:438)49821.tm.p1: 5′-TGCTCTGTTGGCTACGGCTTTAGTCCCTAG-3′ (SEQ ID NO:439) PRO809(DNA57836-1338): 57836.tm.f1: 5′-AGCAGCAGCCATGTAGAATGAA-3′ (SEQ IDNO:440) 57836.tm.r1: 5′-AATACGAACAGTGCACGCTGAT-3′ (SEQ ID NO:441)57836.tm.p1: 5′-TCCAGAGAGCCAAGCACGGCAGA-3′ (SEQ ID NO:442) PRO830(DNA56866-1342): 56866.tm.f1: 5′-TCTAGCCAGCTTGGCTCCAATA-3′ (SEQ IDNO:443) 56866.tm.r1: 5′-CCTGGCTCTAGCACCAACTCATA-3′ (SEQ ID NO:444)56866.tm.p1: 5′-TCAGTGGCCCTAAGGAGATGGGCCT-3′ (SEQ ID NO:445) PRO848(DNA59839-1461): 59839.tm.f1: 5′-CAGGATACAGTGGGAATCTTGAGA-3′ (SEQ IDNO:446) 59839.tm.r1: 5′-CCTGAAGGGCTTGGAGCTTAGT-3′ (SEQ ID NO:447)59839.tm.p1: 5′-TCTTTGGCCATTTCCCATGGCTCA-3′ (SEQ ID NO:448) PRO943(DNA52192-1369): 52192.tm.f1: 5′-CCCATGGCGAGGAGGAAT-3′ (SEQ ID NO:449)52192.tm.r1: 5′-TGCGTACGTGTGCCTTCAG-3′ (SEQ ID NO:450) 52192.tm.p1:5′-CAGCACCCCAGGCAGTCTGTGTGT-3′ (SEQ ID NO:451) PRO1005 (DNA57708-1411):57708.tm.f1: 5′-AACGTGCTACACGACCAGTGTACT-3′ (SEQ ID NO:452) 57708.tm.r1:5′-CACAGCATATTCAGATGACTAAATCCA-3′ (SEQ ID NO:453) 57708.tm.p1:5′-TTGTTTAGTTCTCCACCGTGTCTCCACAGAA-3′ (SEQ ID NO:454) PRO1009(DNA57129-1413): 57129.tm.f1: 5′-TGTCAGAATGCAACCTGGCTT-3′ (SEQ IDNO:455) 57129.tm.r1: 5′-TGATGTGCCTGGCTCAGAAC-3′ (SEQ ID NO:456)57129.tm.p1: 5′-TGCACCTAGATGTCCCCAGCACCC-3′ (SEQ ID NO:457) PRO1097(DNA59841-1460): 59841.tm.f1: 5′-AAGATGCGCCAGGCTTCTTA-3′ (SEQ ID NO:458)59841.tm.r1: 5′-CTCCTGTACGGTCTGCTCACTTAT-3′ (SEQ ID NO:459) 59841.tm.p1:5′-TGGCTGTCAGTCCAGTGTGCATGG-3′ (SEQ ID NO:460) PRO1107 (DNA59606-1471):59606.tm.f1: 5′-GCATAGGGATAGATAAGATCCTGCTTTAT-3′ (SEQ ID NO:461)59606.tm.r1: 5′-CAAATTAAAGTACCCATCAGGAGAGAA-3′ (SEQ ID NO:462)59606.tm.p1: 5′-AAGTTGCTAAATATATACATTATCTGCGCCAAGTCCA-3′ (SEQ ID NO:463)PRO1111 (DNA58721-1475): 58721.tm.f1: 5′-GTGCTGCCCACAATTCATGA-3′ (SEQ IDNO:464) 58721.tm.r1: 5′-GTCCTTGGTATGGGTCTGAATTATAT-3′ (SEQ ID NO:46558721.tm.p1: 5′-ACTCTCTGCACCCCACAGTCACCACTATCTC-3′ (SEQ ID NO:466)PRO1153 (DNA59842-1502): 59842.tm.f1: 5′-CTGAGGAACCAGCCATGTCTCT-3′ (SEQID NO:467) 59842.tm.r1: 5′-GACCAGATGCAGGTACAGGATGA-3′ (SEQ ID NO:468)59842.tm.p1: 5′-CTGCCCCTTCAGTGATGCCAACCTT-3′ (SEQ ID NO:469) PRO1182(DNA59848-1512): 59848.tm.f1: 5′-GGGTGGAGGCTCACTGAGTAGA-3′ (SEQ IDNO:470) 59848.tm.r1: 5′-CAATACAGGTAATGAAACTCTGCTTCTT-3′ (SEQ ID NO:471)59848.tm.p1: 5′-TCCTCTTAAGCATAGGCCATTTTCTCAGTTTAGACA-3′ (SEQ ID NO:472)PRO1184 (DNA59220-1514): 59220.tm.f1: 5′-GGTGGTCTTGCTTGGTCTCAC-3′ (SEQID NO:473) 59220.tm.r1: 5′-CCGTCGTTCAGCAACATGAC-3′ (SEQ ID NO:474)59220.tm.p1: 5′-ACCGCCTACCGCTGTGCCCA-3′ (SEQ ID NO:475) PRO1187(DNA62876-1517): 62876.tm.f1: 5′-CAGTAAAACCACAGGCTGGATTT-3′ (SEQ IDNO:476) 62876.tm.r1: 5′-CCTGAGAGCAAGAAGGTTGAGAAT-3′ (SEQ ID NO:477)62876.tm.p1: 5′-TAGACAGGGACCATGGCCCGCA-3′ (SEQ ID NO:478) PRO1281(DNA59820-1549): 59820.tm.f1: 5′-TGGGCTGTAGAAGAGTTGTTG-3′ (SEQ IDNO:479) 59820.tm.r1: 5′-TCCACACTTGGCCAGTTTAT-3′ (SEQ ID NO:480)59820.tm.p1: 5′-CCCAACTTCTCCCTTTTGGACCCT-3′ (SEQ ID NO:481) PRO1112(DNA57702-1476): 57702.tm.f1 5′-GTCCCTTCACTGTTTAGAGCATGA-3′ (SEQ IDNO:482) 57702.tm.p1 5′-ACTCTCCCCCTCAACAGCCTCCTGAG-3′ (SEQ ID NO:483)57702.tm.r1 5′-GTGGTCAGGGCAGATCCTTT-3′ (SEQ ID NO:484) PRO1185(DNA62881-1515): 62881.tm.f1: 5′-ACAGATCCAGGAGAGACTCCACA-3′ (SEQ IDNO:485) 62881.tm.p1: 5′-AGCGGCGCTCCCAGCCTGAAT-3′ (SEQ ID NO:486)62881.tm.r1: 5′-CATGATTGGTCCTCAGTTCCATC-3′ (SEQ ID NO:487) PRO1245(DNA64884-1527): 64884.tm.f1: 5′-ATAGAGGGCTCCCAGAAGTG-3′ (SEQ ID NO:488)64884.tm.p1: 5′-CAGGGCCTTCAGGGCCTTCAC-3′ (SEQ ID NO:489) 64884.tm.r1:5′-GCTCAGCCAAACACTGTCA-3′ (SEQ ID NO:490) 64884.tm.f2:5′-GGGGCCCTGACAGTGTT-3′ (SEQ ID NO:491) 64884.tm.p2:5′-CTGAGCCGAGACTGGAGCATCTACAC-3′ (SEQ ID NO:492) 64884.tm.r2:5′-GTGGGCAGCGTCTTGTC-3′ (SEQ ID NO:493)

The 5′ nuclease assay reaction is a fluorescent PCR-based techniquewhich makes use of the 5′ exonuclease activity of Taq DNA polymeraseenzyme to monitor amplification in real time. Two oligonucleotideprimers (forward [.f] and reverse [.r]) are used to generate an amplicontypical of a PCR reaction. A third oligonucleotide, or probe (.p), isdesigned to detect nucleotide sequence located between the two PCRprimers. The probe is non-extendible by Taq DNA polymerase enzyme, andis labeled with a reporter fluorescent dye and a quencher fluorescentdye. Any laser-induced emission from the reporter dye is quenched by thequenching dye when the two dyes are located close together as they areon the probe. During the amplification reaction, the Taq DNA polymeraseenzyme cleaves the probe in a template-dependent manner. The resultantprobe fragments disassociate in solution, and signal from the releasedreporter dye is free from the quenching effect of the secondfluorophore. One molecule of reporter dye is liberated for each newmolecule synthesized, and detection of the unquenched reporter dyeprovides the basis for quantitative interpretation of the data.

The 5′ nuclease procedure is run on a real-time quantitative PCR devicesuch as the ABI Prism 7700TM Sequence Detection. The system consists ofa thermocycler, laser, charge-coupled device (CCD) camera and computer.The system amplifies samples in a 96-well format on a thermocycler.During amplification, laser-induced fluorescent signal is collected inreal-time through fiber optics cables for all 96 wells, and detected atthe CCD. The system includes software for running the instrument and foranalyzing the data.

5′ Nuclease assay data are initially expressed as Ct, or the thresholdcycle. This is defined as the cycle at which the reporter signalaccumulates above the background level of fluorescence. The ΔCt valuesare used as quantitative measurement of the relative number of startingcopies of a particular target sequence in a nucleic acid sample whencomparing cancer DNA results to normal human DNA results.

Table 8 describes the stage, T stage and N stage of various primarytumors which were used to screen the PRO polypeptide compounds of theinvention.

TABLE 8 Primary Lung and Colon Tumor Profiles Primary Tumor Stage StageOther Stage Dukes Stage T Stage N Stage Human lung tumor AdenoCa(SRCC724) [LT1] IIA T1 N1 Human lung tumor SqCCa (SRCC725) [LT1a] IIB T3N0 Human lung tumor AdenoCa (SRCC726) [LT2] IB T2 N0 Human lung tumorAdenoCa (SRCC727) [LT3] IIIA T1 N2 Human lung tumor AdenoCa (SRCC728)[LT4] IB T2 N0 Human lung tumor SqCCa (SRCC729) [LT6] IB T2 N0 Humanlung tumor Aden/SqCCa (SRCC730) [LT7] IA T1 N0 Human lung tumor AdenoCa(SRCC731) [LT9] IB T2 N0 Human lung tumor SqCCa (SRCC732) [LT10] IIB T2N1 Human lung tumor SqCCa (SRCC733) [LT11] IIA T1 N1 Human lung tumorAdenoCa (SRCC734) [LT12] IV T2 N0 Human lung tumor AdenoSqCCa (SRCC735)[LT13] IB T2 N0 Human lung tumor SqCCa (SRCC736) [LT15] IB T2 N0 Humanlung tumor SqCCa (SRCC737) [LT16] IB T2 N0 Human lung tumor SqCCa(SRCC738) [LT17] IIB T2 N1 Human lung tumor SqCCa (SRCC739) [LT18] IB T2N0 Human lung tumor SqCCa (SRCC740) [LT19] IB T2 N0 Human lung tumorLCCa (SRCC741) [LT21] IIB T3 N1 Human lung AdenoCa (SRCC811) [LT22] 1AT1 N0 Human colon AdenoCa (SRCC742) [CT2] M1 D pT4 N0 Human colonAdenoCa (SRCC743) [CT3] B pT3 N0 Human colon AdenoCa (SRCC744) [CT8] BT3 N0 Human colon AdenoCa (SRCC745) [CT10] A pT2 N0 Human colon AdenoCa(SRCC746) [CT12] MO, R1 B T3 N0 Human colon AdenoCa (SRCC747) [CT14]pMO, RO B pT3 pN0 Human colon AdenoCa (SRCC748) [CT15] M1, R2 D T4 N2Human colon AdenoCa (SRCC749) [CT16] pMO B pT3 pN0 Human colon AdenoCa(SRCC750) [CT17] C1 pT3 pN1 Human colon AdenoCa (SRCC751) [CT1] MO, R1 BpT3 N0 Human colon AdenoCa (SRCC752) [CT4] B pT3 M0 Human colon AdenoCa(SRCC753) [CT5] G2 C1 pT3 pN0 Human colon AdenoCa (SRCC754) [CT6] pMO,RO B pT3 pN0 Human colon AdenoCa (SRCC755) [CT7] G1 A pT2 pN0 Humancolon AdenoCa (SRCC756) [CT9] G3 D pT4 pN2 Human colon AdenoCa (SRCC757)[CT11] B T3 N0 Human colon AdenoCa (SRCC758) [CT18] MO, RO B pT3 pN0DNA Preparation

DNA was prepared from cultured cell lines, primary tumors, normal humanblood. The isolation was performed using purification kit, buffer setand protease and all from Quiagen, according to the manufacturer'sinstructions and the description below.

Cell Culture Lysis:

Cells were washed and trypsinized at a concentration of 7.5×10⁸ per tipand pelleted by centrifuging at 1000 rpm for 5 minutes at 4° C.,followed by washing again with ½ volume of PBS recentrifugatio pelletswere washed a third time, the suspended cells collected and washed 2×with PBS. The cells were then suspended into 10 ml PBS. Buffer C1 wasequilibrated at 4° C. Qiagen protease #19155 was diluted into 6.25 mlcold ddH₂O to a final concentration of 20 mg/ml and equilibrated at 4°C. 10 ml of G2 Buffer was prepared by diluting Qiagen RNAse A stock (100mg/ml) to a final concentration of 200 μg/ml.

Buffer C1 (10 ml, 4° C.) and ddH2O (40 ml, 4° C) were then added to the10 ml of cell suspension, mixed by inverting and incubated on ice for 10minutes. The cell nuclei were pelleted by centrifuging in a Beckmanswinging bucket rotor at 2500 rpm at 4° C. for 15 minutes. Thesupernatant was discarded and the nuclei were suspended with a vortexinto 2 ml Buffer C1 (at 4° C.) and 6 ml ddH₂O, followed by a second 4°C. centrifugation at 2500 rpm for 15 minutes. The nuclei were thenresuspended into the residual buffer using 200 μl per tip. G2 buffer (10ml) was added to the suspended nuclei while gentle vortexing wasapplied. Upon completion of buffer addition, vigorous vortexing wasapplied for 30 seconds. Quiagen protease (200 μl, prepared as indicatedabove) was added and incubated at 50° C. for 60 minutes. The incubationand centrifugation was repeated until the lysates were clear (e.g.,incubating additional 30–60 minutes, pelleting at 3000×g for 10 min., 4°C.).

Solid Human Tumor Sample Preparation and Lysis:

Tumor samples were weighed and placed into 50 ml conical tubes and heldon ice. Processing was limited to no more than 250 mg tissue perpreparation (1 tip/preparation). The protease solution was freshlyprepared by diluting into 6.25 ml cold ddH₂O to a final concentration of20 mg/ml and stored at 4° C. G2 buffer (20 ml) was prepared by dilutingDNAse A to a final concentration of 200 mg/ml (from 100 mg/ml stock).The tumor tissue was homogenated in 19 ml G2 buffer for 60 seconds usingthe large tip of the polytron in a laminar-flow TC hood in order toavoid inhalation of aerosols, and held at room temperature. Betweensamples, the polytron was cleaned by spinning at 2×30 seconds each in 2LddH₂O, followed by G2 buffer (50 ml). If tissue was still present on thegenerator tip, the apparatus was disassembled and cleaned.

Quiagen protease (prepared as indicated above, 1.0 ml) was added,followed by vortexing and incubation at 50° C. for 3 hours. Theincubation and centrifugation was repeated until the lysates were clear(e.g., incubating additional 30–60 minutes, pelleting at 3000×g for 10min., 4° C.).

Human Blood Preparation and Lysis:

Blood was drawn from healthy volunteers using standard infectious agentprotocols and citrated into 10 ml samples per tip. Quiagen protease wasfreshly prepared by dilution into 6.25 ml cold ddH₂O to a finalconcentration of 20 mg/ml and stored at 4° C. G2 buffer was prepared bydiluting RNAse A to a final concentration of 200 μg/ml from 100 mg/mlstock. The blood (10 ml) was placed into a 50 ml conical tube and 10 mlC1 buffer and 30 ml ddH₂O (both previously equilibrated to 4° C.) wereadded, and the component mixed by inverting and held on ice for 10minutes. The nuclei were pelleted with a Beckman swinging bucket rotorat 2500 rpm, 4° C. for 15 minutes and the supernatant discarded. With avortex, the nuclei were suspended into 2 ml C1 buffer (4° C.) and 6 mlddH₂O (4° C). Vortexing was repeated until the pellet was white. Thenuclei were then suspended into the residual buffer using a 200 μl tip.G2 buffer (10 ml) were added to the suspended nuclei while gentlyvortexing, followed by vigorous vortexing for 30 seconds. Quiagenprotease was added (200 μl) and incubated at 50° C. for 60 minutes. Theincubation and centrifugation was repeated until the lysates were clear(e.g., incubating additional 30–60 minutes, pelleting at 3000×g for 10min., 4° C.)

Purification of Cleared Lysates:

(1) Isolation of Genomic DNA:

Genomic DNA was equilibrated (1 sample per maxi tip preparation) with 10ml QBT buffer. QF elution buffer was equilibrated at 50° C. The sampleswere vortexed for 30 seconds, then loaded onto equilibrated tips anddrained by gravity. The tips were washed with 2×15 ml QC buffer. The DNAwas eluted into 30 ml silanized, autoclaved 30 ml Corex tubes with 15 mlQF buffer (50° C). Isopropanol (10.5 ml) was added to each sample, thetubes covered with parafin and mixed by repeated inversion until the DNAprecipitated. Samples were pelleted by centrifugation in the SS-34 rotorat 15,000 rpm for 10 minutes at 4° C. The pellet location was marked,the supernatant discarded, and 10 ml 70% ethanol (4° C.) was added.Samples were pelleted again by centrifugation on the SS-34 rotor at10,000 rpm for 10 minutes at 4° C. The pellet location was marked andthe supernatant discarded. The tubes were then placed on their side in adrying rack and dried 10 minutes at 37° C., taking care not to overdrythe samples.

After drying, the pellets were dissolved into 1.0 ml TE (pH 8.5) andplaced at 50° C. for 1–2 hours. Samples were held overnight at 4° C. asdissolution continued. The DNA solution was then transferred to 1.5 mltubes with a 26 gauge needle on a tuberculin syringe. The transfer wasrepeated 5× in order to shear the DNA. Samples were then placed at 50°C. for 1–2 hours.

(2) Quantitation of Genomic DNA and Preparation for Gene AmplificationAssay:

The DNA levels in each tube were quantified by standard A₂₆₀, A₂₈₀spectrophotometry on a 1:20 dilution (5 μl DNA+95 μl ddH₂O) using the0.1 ml quartz cuvetts in the Beckman DU640 spectrophotometer. A₂₆₀/A₂₈₀ratios were in the range of 1.8–1.9. Each DNA samples was then dilutedfurther to approximately 200 ng/ml in TE (pH 8.5). If the originalmaterial was highly concentrated (about 700 ng/μl), the material wasplaced at 50° C. for several hours until resuspended.

Fluorometric DNA quantitation was then performed on the diluted material(20–600 ng/ml) using the manufacturer's guidelines as modified below.This was accomplished by allowing a Hoeffer DyNA Quant 200 fluorometerto warm-up for about 15 minutes. The Hoechst dye working solution(#H33258, 10 μl, prepared within 12 hours of use) was diluted into 100ml 1×TNE buffer. A 2 ml cuvette was filled with the fluorometersolution, placed into the machine, and the machine was zeroed. pGEM3Zf(+) (2 μl, lot #360851026) was added to 2 ml of fluorometer solutionand calibrated at 200 units. An additional 2 μl of pGEM 3Zf(+) DNA wasthen tested and the reading confirmed at 400 +/−10 units. Each samplewas then read at least in triplicate. When 3 samples were found to bewithin 10% of each other, their average was taken and this value wasused as the quantification value.

The fluorometricly determined concentration was then used to dilute eachsample to 10 ng/μl in ddH₂O. This was done simultaneously on alltemplate samples for a single TaqMan plate assay, and with enoughmaterial to run 500–1000 assays. The samples were tested in triplicatewith Taqman™ primers and probe both B-actin and GAPDH on a single platewith normal human DNA and no-template controls. The diluted samples wereused provided that the CT value of normal human DNA subtracted from testDNA was +/−1 Ct. The diluted, lot-qualified genomic DNA was stored in1.0 ml aliquots at −80° C. Aliquots which were subsequently to be usedin the gene amplification assay were stored at 4° C. Each 1 ml aliquotis enough for 8–9 plates or 64 tests.

Gene Amplification Assay

The PRO polypeptide compounds of the invention were screened in thefollowing primary tumors and the resulting ΔCt values greater than orequal to 1.0 are reported in Tables 9A–C below.

TABLE 9A ΔCt values in lung and colon primary tumors and cell linemodels Primary Tumor PRO290 PRO341 PRO535 PRO619 PRO1112 PRO809 PRO830PRO848 LT-1a — — — — — — 1.13 — LT3 — — — 1.04 — — — — 1.68 LT7 — — —1.21 — — — — 1.34 LT9 — — — 1.19 — — — — 1.34 LT10 — — — 1.41 1.135 — —— 2.02 LT11 1.63 — 1.40 1.69 1.525 1.40 1.25 1.04 1.57 LT12 — — — 1.811.195 1.61 1.35 1.22 LT13 1.47 — 1.37 2.13 1.635 1.03 — — 1.74 LT15 1.67— — 2.08 1.775 — — — 1.52 LT16 — 1.12 — — — — — — LT17 1.22 1.33 1.421.83 1.455 1.10 1.17 — 1.67 LT18 — — — 1.32 1.255 — — — 1.14 LT19 2.07 —— 2.33 — — 1.31 — 1.90 LT21 — 1.15 — 1.15 — 1.05 — 1.07 1.09 CT2 1.56 —— 1.22 2.265 — — — CT3 — — 1.28 1.49 — — — — CT8 — — — — 1.065 — — —CT10 — — 1.34 — 1.575 — — — CT12 — — — — 1.315 — — — CT14 — — 1.29 —1.895 — — — CT15 — — 1.10 1.00 1.465 — — — CT16 — — 1.35 1.02 1.255 — —— CT17 — — 1.26 1.23 — — — — CT1 — — — 1.12 1.245 — — — CT4 — — 1.031.25 1.535 — — — CT5 — — — 1.34 1.975 — — — CT6 — — 1.00 1.06 1.575 — —— CT11 1.16 — 1.25 1.80 2.285 — — —

TABLE 9B ΔCt values in lung and colon primary tumors and cell linemodels Primary Tumor PRO943 PRO1005 PRO1009 PRO1185 PRO1245 PRO1097PRO1107 PRO1111 PRO1153 LT-1 — 1.07 — — — — — — — LT-1a — 3.87 — — — — —— — LT2 — — — — — 1.23 — — — LT3 — 1.61 — 1.01 — — — 1.39 — LT4 — — — —— — — 1.49 1.01 LT6 — 1.29 — — — — — — — LT7 — — — — — — — 1.58 1.52 LT9— 2.50 — — — 1.21 — 1.44 — LT10 — — — — — — — 1.05 — LT11 2.06 — — — — —— 1.45 — LT12 1.94 1.21 — — — — — — — LT13 1.64 2.30 — — 3.84 — 3.55 — —1.27 LT15 2.05 1.03 — — 1.01 — 2.47 — — LT16 — 1.05 — — 1.98 — 2.45 — —LT17 1.93 — — — — — — 1.47 — LT19 2.90 — — — — — — — — LT26 — — — 1.66 —— — — — LT30 — — — 1.58 — — — — — CT2 1.92 — 2.00 1.73 — — 4.75 — — 1.70CT3 — — 1.75 — — — 1.52 — — CT8 1.37 — 1.29 — — — — — — 1.12 CT10 2.13 —1.73 — — — 2.82 — — 1.67 CT12 1.43 — 1.92 — — — — — — CT14 1.46 — 2.10 —— 1.08 1.54 1.38 — CT15 — — 2.02 — 1.00 — — — — CT16 — — 1.56 — — 1.11 —— — CT17 1.30 — 1.76 — — 1.34 — — — CT1 1.36 — — — — — 1.57 — — CT4 — —1.06 — — — 1.59 — — CT5 1.88 — 1.43 — — — — — — 2.51 CT6 1.41 — — — — —— — — 1.75 CT7 — — — — — — — 1.16 — CT11 2.80 — 1.83 — — — — 1.17 — 2.61CT18 1.30 — — — — — — 1.05 — H522 — — — — 1.10 — — —

TABLE 9C ΔCt values in lung and colon primary tumors and cell linemodels Primary Tumor PRO1182 PRO1184 PRO1187 PRO1281 LT-1 1.81 — — —LT-1a — 1.14 — — 1.09 LT4 1.43 1.37 — — 1.18 LT6 — 1.78 — — 1.66 1.05LT9 1.43 — — LT12 — 2.47 1.17 — 2.61 1.80 LT15 — — 1.55 — LT16 — 1.011.33 — LT17 — — — — LT18 — 1.07 — — 1.13 LT19 — 1.19 — — 1.35 1.02 LT21— 1.00 — — 1.20 CT2 — — — 1.15 CT12 — — — 1.07

Because amplification of the various DNAs described above occurs invarious cancerous tumors and tumor cell lines derived from various humantissues, these molecules likely play a significant role in tumorformation and/or growth. As a result, amplification and/or enhancedexpression of these molecules can serve as a diagnostic for detectingthe presence of tumor in an individual and antagonists (e.g.,antibodies) directed against the proteins encoded by the above describedDNA molecules would be expected to have utility in cancer therapy.

Example 171 Identification of Receptor/Ligand Interactions

In this assay, various PRO polypeptides are tested for ability to bindto a panel of potential receptor molecules for the purpose ofidentifying receptor/ligand interactions. The identification of a ligandfor a known receptor, a receptor for a known ligand or a novelreceptor/ligand pair is useful for a variety of indications including,for example, targeting bioactive molecules (linked to the ligand orreceptor) to a cell known to express the receptor or ligand, use of thereceptor or ligand as a reagent to detect the presence of the ligand orreceptor in a composition suspected of containing the same, wherein thecomposition may comprise cells suspected of expressing the ligand orreceptor, modulating the growth of or another biological orimmunological activity of a cell known to express or respond to thereceptor or ligand, modulating the immune response of cells or towardcells that express the receptor or ligand, allowing the preparation ofagonists, antagonists and/or antibodies directed against the receptor orligand which will modulate the growth of or a biological orimmunological activity of a cell expressing the receptor or ligand, andvarious other indications which will be readily apparent to theordinarily skilled artisan.

The assay is performed as follows. A PRO polypeptide of the presentinvention suspected of being a ligand for a receptor is expressed as afusion protein containing the Fc domain of human IgG (an immunoadhesin).Receptor-ligand binding is detected by allowing interaction of theimmunoadhesin polypeptide with cells (e.g. Cos cells) expressingcandidate PRO polypeptide receptors and visualization of boundimmunoadhesin with fluorescent reagents directed toward the Fc fusiondomain and examination by microscope. Cells expressing candidatereceptors are produced by transient transfection, in parallel, ofdefined subsets of a library of cDNA expression vectors encoding PROpolypeptides that may function as receptor molecules. Cells are thenincubated for 1 hour in the presence of the PRO polypeptideimmunoadhesin being tested for possible receptor binding. The cells arethen washed and fixed with paraformaldehyde. The cells are thenincubated with fluorescent conjugated antibody directed against the Fcportion of the PRO polypeptide immunoadhesin (e.g. FITC conjugated goatanti-human-Fc antibody). The cells are then washed again and examined bymicroscope. A positive interaction is judged by the presence offluorescent labeling of cells transfected with cDNA encoding aparticular PRO polypeptide receptor or pool of receptors and an absenceof similar fluorescent labeling of similarly prepared cells that havebeen transfected with other cDNA or pools of cDNA. If a defined pool ofcDNA expression vectors is judged to be positive for interaction with aPRO polypeptide immunoadhesin, the individual cDNA species that comprisethe pool are tested individually (the pool is “broken down”) todetermine the specific cDNA that encodes a receptor able to interactwith the PRO polypeptide immunoadhesin.

In another embodiment of this assay, an epitope-tagged potential ligandPRO polypeptide (e.g. 8 histidine “His” tag) is allowed to interact witha panel of potential receptor PRO polypeptide molecules that have beenexpressed as fusions with the Fc domain of human IgG (immunoadhesins).Following a 1 hour co-incubation with the epitope tagged PROpolypeptide, the candidate receptors are each immunoprecipitated withprotein A beads and the beads are washed. Potential ligand interactionis determined by western blot analysis of the immunoprecipitatedcomplexes with antibody directed towards the epitope tag. An interactionis judged to occur if a band of the anticipated molecular weight of theepitope tagged protein is observed in the western blot analysis with acandidate receptor, but is not observed to occur with the other membersof the panel of potential receptors.

Using these assays, the following receptor/ligand interactions have beenherein identified:

-   (1) PRO943 binds to FHF1, PRO183 (FHF2), PRO184 (FHF3) and PRO185    (FHF4) and vice versa.-   (2) PRO331 binds to PRO1133 and vice versa.-   (3) PRO363 binds to PRO1387 and vice versa.-   (4) PRO5723 binds to PRO1387 and vice versa.-   (5) PRO1114 binds to PRO3301 and PRO9940 and vice versa.-   (6) PRO9828 appears to be a novel fibroblast growth factor receptor    (FGFR) ligand in that it binds to the known FGF receptors FGFR1,    FGFR2IIIC, FGFR3IIIC and FGFR4. PRO9828 and agonists, therefore,    will find use for activating the biological activities normally    activated by FGF molecules including, for example, cell growth and    proliferation. Antagonists of PRO9828 will find use in blocking the    biological activities mediated through the FGF receptor.-   (7) PRO1181 binds to PRO7170, PRO361 and PRO846.

Example 172 Tissue Expression Distribution

Oligonucleotide probes were constructed from the PROpolypeptide-encoding nucleotide sequences shown in the figures for usein quantitative PCR amplification reactions. The oligonucleotide probeswere chosen so as to give an approximately 200–600 base pair amplifiedfragment from the 3′ end of its associated template in a standard PCRreaction. The oligonucleotide probes were employed in standardquantitative PCR amplification reactions with cDNA libraries isolatedfrom different human adult and/or fetal tissue sources and analyzed byagarose gel electrophoresis so as to obtain a quantitative determinationof the level of expression of the PRO polypeptide-encoding nucleic acidsin the various tissues tested. Knowledge of the expression pattern orthe differential expression of the PRO polypeptide-encoding nucleicacids in various different human tissue types provides a diagnosticmarker useful for tissue typing, with or without other tissue-specificmarkers, for determining the primary tissue source of a metastatictumor, disease diagnosis, and the like. These assays provided thefollowing results.

DNA Molecule Tissues w/Significant Expression Tissues w/o SignificantExpression DNA16422-1209 substantia nigra, dendrocytes, uterushippocampus DNA16435-1208 substantia nigra, dendrocytes, uterushippocampus DNA26843-1389 dendrocytes, heart, uterus, colon tumorhippocampus, substantia nigra, cartilage DNA26844-1394 HUVEC,dendrocytes, cartilage substantia nigra, hippocampus, uterus, prostateDNA40621-1440 prostate, uterus, colon tumor brain, heart, HUVEC,cartilage DNA44161-1434 colon tumor, dendrocytes substantia nigra,hippocampus, prostate, uterus DNA44694-1500 dendrocytes, hippocampus,prostate colon tumor, substantia nigra, heart DNA48320-1433 prostate,uterus colon tumor, brain, heart, cartilage DNA49647-1398 brain, heart,prostate, uterus cartilage DNA53913-1490 hippocampus substantia nigra,dendrocytes DNA53978-1443 dendrocytes, uterus, prostate substantianigra, colon tumor DNA53996-1442 spleen, prostate, uterus, hippocampussubstantia nigra, heart DNA56050-1455 prostate, uterus, cartilage,hippocampus heart, colon tumor, dendrocytes DNA56110-1437 spleen, colontumor, brain, prostate heart DNA56410-1414 uterus, dendrocyteshippocampus, substantia nigra, heart DNA56436-1448 substantia nigra,prostate, hippocampus dendrocytes, heart, HUVEC DNA56855-1447 prostate,uterus brain, cartilage, heart, colon tumor DNA56860-1510 colon tumorprostate, uterus, dendrocytes DNA56868-1478 colon tumor, prostateuterus, brain, heart, cartilage DNA56869-1545 prostate, uterus,cartilage brain, colon tumor, spleen, heart DNA57699-1412 dendrocytes,hippocampus, prostate sunstantia nigra, heart DNA57704-1452 brain,heart, spleen, uterus, prostate colon tumor DNA57710-1451 dendrocytes,hippocampus, spleen, uterus substantia nigra, heart DNA57711-1501dendrocytes, hippocampus, heart, cartilage substantia nigraDNA57827-1493 colon tumor, hippocampus, prostate sunstantia nigra,dendrocytes, uterus DNA58723-1588 substantia nigra, cartilage uterushippocampus, dendrocytes, HUVEC DNA58743-1609 brain, prostate, uteruscolon tumor, heart, spleen, cartilage DNA58846-1409 hippocampus,dendrocytes substantia nigra, uterus, prostate, colon tumorDNA58849-1494 prostate brain, uterus, cartilage, heart, colon tumorDNA58850-1495 spleen, prostate, dendrocytes hippocampus, substantianigra, colon tumor DNA59213-1487 spleen, cartilage, prostate, substantianigra heart, hippocampus, dendrocytes DNA59497-1496 dendrocytes,prostate, uterus, heart cartilage, hippocampus, substantia nigraDNA59605-1418 dendrocytes, prostate, uterus hippocampus, substantianigra, colon tumor DNA59609-1470 dendrocytes substantia nigra,hippocampus, heart, prostate, uterus, spleen DNA59612-1466 prostate,dendrocytes hippocampus, substantia nigra, uterus, colon tumorDNA59616-1465 dendrocytes, substantia nigra, colon tumor hippocampusDNA59619-1464 dendrocytes, substantia nigra, colon tumor hippocampusDNA59625-1498 brain, colon tumor, prostate, uterus THP-1 macrophagesDNA59827-1426 substantia nigra, prostate, uterus hippocampus,dendrocytes, heart DNA59828-1608 dendrocytes, substantia nigra, colontumor hippocampus DNA59853-1505 prostate brain, uterus, spleen, heart,colon tumor DNA59854-1459 cartilage prostate, brain, heart, colon tumorDNA60283-1484 dendrocytes, spleen, prostate, uterus hippocampus,substantia nigra, heart DNA60619-1482 dendrocytes, substantia nigra,colon tumor hippocampus DNA60625-1507 cartilaqge prostate, brain, heart,colon tumor DNA60629-1481 uterus, colon tumor, substantia nigrahippocampus, dendrocytes, spleen, prostate DNA61755-1554 dendrocytes,substantia nigra, colon tumor hippocampus DNA64852-1589 prostate, uterusbrain, heart, cartilage, colon tumor DNA66308-1537 prostate, heartuterus brain, colon tumor, cartilage DNA68869-1610 spleen, prostate,heart, uterus, colon hippocampus, dendrocytes, prostate tumor,substantia nigra

Example 173 Isolation of cDNA Clones Encoding Human PRO846

A consensus sequence was obtained relative to a variety of EST sequencesas described in Example 1 above, wherein the consensus sequence obtainedis herein designated DNA39949. Based on the DNA39949 consensus sequence,oligonucleotides were synthesized: 1) to identify by PCR a cDNA librarythat contained the sequence of interest, and 2) for use as probes toisolate a clone of the full-length coding sequence for PRO846.

Forward and reverse PCR primers were synthesized:

forward PCR primer 5′-CCCTGCAGTGCACCTACAGGGAAG-3′ (SEQ ID NO:518)reverse PCR primer 5′-CTGTCTTCCCCTGCTTGGCTGTGG-3′ (SEQ ID NO:519)Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the consensus DNA39949 sequence which had the followingnucleotide sequenceHybridization Probe

-   5′-GGTGCAGGAAGGGTGGGATCCTCTTCTCTCGCTGCTCTGGCCACATC-3′ (SEQ ID    NO:520)

In order to screen several libraries for a source of a full-lengthclone, DNA from the libraries was screened by PCR amplification with oneof the PCR primer pairs identified above. A positive library was thenused to isolate clones encoding the PRO846 gene using the probeoligonucleotide and one of the PCR primers. RNA for construction of thecDNA libraries was isolated from human fetal kidney tissue (LIB227).

DNA sequencing of the clones isolated as described above gave thefull-length DNA sequence for PRO846 [herein designated as DNA44196-1353](SEQ ID NO:516) and the derived protein sequence for PRO846.

The entire nucleotide sequence of UNQ422 (DNA44196-1353) is shown inFIG. 329 (SEQ ID NO:516). Clone UNQ422 (DNA44196-1353) contains a singleopen reading frame with an apparent translational initiation site atnucleotide positions 25–27 and ending at the stop codon at nucleotidepositions 1021–1023 (FIG. 329). The predicted polypeptide precursor is332 amino acids long (FIG. 330). The full-length PRO846 protein shown inFIG. 330 has an estimated molecular weight of about 36,143 daltons and apI of about 5.89. Important regions of the amino acid sequence of PRO846include the signal peptide, the transmembrane domain, an N-glycosylationsite, a sequence typical of fibrinogen beta and gamma chains C-terminaldomain, and a sequence typical of Ig like V-type domain as shown in FIG.330. Clone UNQ422 (DNA44196-1353) has been deposited with ATCC and isassigned ATCC deposit no. 209847.

Example 174 Isolation of cDNA Clones Encoding Human PRO363

A consensus sequence was obtained relative to a variety of EST sequencesas described in Example 1 above, wherein the consensus sequence obtainedis herein designated DNA42828. Based on the DNA42828 consensus sequence,oligonucleotides were synthesized: 1) to identify by PCR a cDNA librarythat contained the sequence of interest, and 2) for use as probes toisolate a clone of the full-length coding sequence for PRO363.

A pair of PCR primers (forward and reverse) were synthesized:

forward PCR primer (42828.fl) 5′-CCAGTGCACAGCAGGCAACGAAGC-3′ (SEQ IDNO:521) reverse PCR primer (42828.rl) 5′-ACTAGGCTGTATGCCTGGGTGGGC-3′(SEQ ID NO:522)Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the consensus DNA42828 sequence which had the followingnucleotide sequenceHybridization Probe (42828.p1)

-   5′-GTATGTACAAAGCATCGGCATGGTTGCAGGAGCAGTGACAGGC-3′ (SEQ ID NO:523)

In order to screen several libraries for a source of a full-lengthclone, DNA from the libraries was screened by PCR amplification with thePCR primer pair identified above. A positive library was then used toisolate clones encoding the PRO363 gene using the probe oligonucleotideand one of the PCR primers. RNA for construction of the cDNA librarieswas isolated from human fetal kidney tissue (LIB227).

DNA sequencing of the clones isolated as described above gave thefull-length DNA sequence for PRO363 [herein designated as UNQ318(DNA45419-1252)] (SEQ ID NO:500) and the derived protein sequence forPRO363.

The entire nucleotide sequence of UNQ318 (DNA45419-1252) is shown inFIG. 313 (SEQ ID NO:500). Clone UNQ318 (DNA45419-1252) contains a singleopen reading frame with an apparent translational initiation site atnucleotide positions 190–192 and ending at the stop codon at nucleotidepositions 1309–1311 (FIG. 313). The predicted polypeptide precursor is373 amino acids long (FIG. 314). The full-length PRO363 protein shown inFIG. 314 has an estimated molecular weight of about 41,281 daltons and apI of about 8.33. A transmembrane domain exists at amino acids 221 to254 of the amino acid sequence shown in FIG. 314 (SEQ ID NO:501). ThePRO363 polypeptide also possesses at least two myelin P0 protein domainsfrom about amino acids 15 to 56 and from about amino acids 87 to 116.Clone UNQ318 (DNA45419-1252) has been deposited with ATCC on Feb. 5,1998 and is assigned ATCC deposit no. 209616.

Analysis of the amino acid sequence of the full-length PRO363polypeptide suggests that it possesses significant sequence similarityto the cell surface protein HCAR, thereby indicating that PRO363 may bea novel HCAR homolog. More specifically, an analysis of the Dayhoffdatabase (version 35.45 SwissProt 35) evidenced significant homologybetween the PRO363 amino acid sequence and the following Dayhoffsequences, HS46KDA_(—)1, HSU90716_(—)1, MMCARH_(—)1, MMCARHOM_(—)1,MMU90715_(—)1, A33_HUMAN, P_W14146, P_W14158, A42632 and B42632.

Example 175 Isolation of cDNA Clones Encoding a Human PRO9828

A consensus DNA sequence was assembled relative to other nucleicsequences using phrap as described in Example 1 above. This consensussequence is herein designated DNA139814. Based on the DNA139814consensus sequence, oligonucleotides were synthesized: 1) to identify byPCR a cDNA library that contained the sequence of interest, and 2) foruse as probes to isolate a clone of the full-length coding sequence forPRO9828. Forward and

-   reverse PCR primers generally range from 20 to 30 nucleotides and    are often designed to give a PCR product of about 100–1000 bp in    length. The probe sequences are typically 40–55 bp in length. In    some cases, additional oligonucleotides are synthesized when the    consensus sequence is greater than about 1–1.5 kbp. In order to    screen several libraries for a full-length clone, DNA from the    libraries was screened by PCR amplification, as per Ausubel et al.,    Current Protocols in Molecular Biology, supra, with the PCR primer    pair. A positive library was then used to isolate clones encoding    the gene of interest using the probe oligonucleotide and one of the    primer pairs.

PCR primers (forward and reverse) were synthesized:

5′-AATCTCAGCACCAGCCACTCAGAGCA-3′ (SEQ ID NO:524)5′-GTTAAAGAGGGTGCCCTTCCAGCGA-3′ (SEQ ID NO:525)5′-TATCCCAATGCCTCCCCACTGCTC-3′ (SEQ ID NO:526)5′-GATGAACTTGGCGAAGGGGCGGCA-3′ (SEQ ID NO:527)

RNA for construction of the cDNA libraries was isolated from human fetalliver tissue. The cDNA libraries used to isolate the cDNA clones wereconstructed by standard methods using commercially available reagentssuch as those from Invitrogen, San Diego, Calif. The cDNA was primedwith oligo dT containing a NotI site, linked with blunt to SalIhemikinased adaptors, cleaved with NotI, sized appropriately by gelelectrophoresis, and cloned in a defined orientation into a suitablecloning vector (such as pRKB or pRKD; pRK5B is a precursor of pRK5D thatdoes not contain the SfiI site; see, Holmes et al., Science,253:1278–1280 (1991)) in the unique XhoI and NotI sites.

DNA sequencing of the clones isolated as described above gave thefull-length DNA sequence for a full-length PRO9828 polypeptide(designated herein as DNA142238-2768 [FIG. 323, SEQ ID NO:510]) and thederived protein sequence for that PRO9828 polypeptide.

The full length clone identified above contained a single open readingframe with an apparent translational initiation site at nucleotidepositions 232–234 and a stop signal at nucleotide positions 985–987(FIG. 323, SEQ ID NO:510). The predicted polypeptide precursor is 251amino acids long, has a calculated molecular weight of approximately27,954 daltons and an estimated pI of approximately 9.22. Analysis ofthe full-length PRO9828 sequence shown in FIG. 324 (SEQ ID NO:511)evidences the presence of a variety of important polypeptide domains asshown in FIG. 324, wherein the locations given for those importantpolypeptide domains are approximate as described above. Chromosomemapping evidences that the PRO9828-encoding nucleic acid maps tochromosome 12p13 in humans. Clone DNA142238-2768 has been deposited withATCC on Oct. 5, 1999 and is assigned ATCC deposit no. 819-PTA.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usingthe ALIGN-2 sequence alignment analysis of the full-length sequenceshown in FIG. 324 (SEQ ID NO:511), evidenced sequence identity betweenthe PRO9828 amino acid sequence and the following Dayhoff sequences:P_Y08581, AB018122_(—)1, FGF3_HUMAN, P_R70824, S54407, P_R80780,P_Y23761, P_W92312, OMFGF6_(—)1 and P_R80871.

Example 176 Isolation of cDNA Clones Encoding a Human PRO7170

DNA108722-2743 was identified by applying a proprietary signal sequencefinding algorithm developed by Genentech, Inc. (South San Francisco,Calif.) upon ESTs as well as clustered and assembled EST fragments frompublic (e.g., Genbank) and/or private (LIFESEQ®, Incyte Pharmaceuticals,Inc., Palo Alto, Calif.) databases. The signal sequence algorithmcomputes a secretion signal score based on the character of the DNAnucleotides surrounding the first and optionally the second methioninecodon(s) (ATG) at the 5′-end of the sequence or sequence fragment underconsideration. The nucleotides following the first ATG must code for atleast 35 unambiguous amino acids without any stop codons. If the firstATG has the required amino acids, the second is not examined. If neithermeets the requirement, the candidate sequence is not scored. In order todetermine whether the EST sequence contains an authentic signalsequence, the DNA and corresponding amino acid sequences surrounding theATG codon are scored using a set of seven sensors (evaluationparameters) known to be associated with secretion signals.

Use of the above described signal sequence algorithm allowedidentification of an EST cluster sequence from the LIFESEQ® database,Incyte Pharmaceuticals, Palo Alto, designated herein as CLU57836. ThisEST cluster sequence was then compared to a variety of expressedsequence tag (EST) databases which included public EST databases (e.g.,Genbank) and a proprietary EST DNA database (LIFESEQ®, IncytePharmaceuticals, Palo Alto, Calif.) to identify existing homologies. Thehomology search was performed using the computer program BLAST or BLAST2(Altshul et al., Methods in Enzymology 266:460–480 (1996)). Thosecomparisons resulting in a BLAST score of 70 (or in some cases 90) orgreater that did not encode known proteins were clustered and assembledinto a consensus DNA sequence with the program “phrap” (Phil Green,University of Washington, Seattle, Wash.). The consensus sequenceobtained therefrom is herein designated DNA58756.

In light of an observed sequence homology between the DNA58756 sequenceand an EST sequence encompassed within clone no. 2251462 from theLIFESEQ® database, Incyte Pharmaceuticals, Palo Alto, Calif., clone no.2251462 was purchased and the cDNA insert was obtained and sequenced. Itwas found herein that that cDNA insert encoded a full-length protein.The sequence of this cDNA insert is shown in FIG. 325 and is hereindesignated as DNA 108722-2743.

Clone DNA108722-2743 contains a single open reading frame with anapparent translational initiation site at nucleotide positions 60–62 andending at the stop codon at nucleotide positions 1506–1508 (FIG. 325).The predicted polypeptide precursor is 482 amino acids long (FIG. 326).The full-length PRO7170 protein shown in FIG. 326 has an estimatedmolecular weight of about 49,060 daltons and a pI of about 4.74.Analysis of the full-length PRO7170 sequence shown in FIG. 326 (SEQ IDNO:513) evidences the presence of a variety of important polypeptidedomains as shown in FIG. 326, wherein the locations given for thoseimportant polypeptide domains are approximate as described above. CloneDNA108722-2743 has been deposited with ATCC on Aug. 17, 1999 and isassigned ATCC Deposit No. 552-PTA.

An analysis of the Dayhoff database (version 35.45 SwissProt 35), usingthe ALIGN-2 sequence alignment analysis of the full-length sequenceshown in FIG. 326 (SEQ ID NO:513), evidenced sequence identity betweenthe PRO7170 amino acid sequence and the following Dayhoff sequences:P_Y12291, I47141, D88733_(—)1, DMC56G7_(—)1, P_Y11606, HWP1_CANAL,HSMUC5BEX_(—)1, HSU78550_(—)1, HSU70136_(—)1, and SGS3_DROME.

Example 177 Isolation of cDNA Clones Encoding Human PRO361

A consensus DNA sequence was assembled relative to other EST sequencesusing phrap as described in Example 1 above. This consensus sequence isherein designated DNA40654. Based on the DNA40654 consensus sequence,oligonucleotides were synthesized: 1) to identify by PCR a cDNA librarythat contained the sequence of interest, and 2) for use as probes toisolate a clone of the full-length coding sequence for PRO361.

Forward and reverse PCR primers were synthesized as follows:

forward PCR primer 5′-AGGGAGGATTATCCTTGACCTTTGAAGACC-3′ (SEQ ID NO:528)forward PCR primer 5′-GAAGCAAGTGCCCAGCTC-3′ (SEQ ID NO:529) forward PCRprimer 5′-CGGGTCCCTGCTCTTTGG-3′ (SEQ ID NO:530) reverse PCR primer5′-CACCGTAGCTGGGAGCGCACTCAC-3′ (SEQ ID NO:531) reverse PCR primer5′-AGTGTAAGTCAAGCTCCC-3′ (SEQ ID NO:532)

Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the consensus DNA40654 sequence which had the followingnucleotide sequence

Hybridization Probe

-   5′-GCTTCCTGACACTAAGGCTGTCTGCTAGTCAGAATTGCCTCAAAAAGAG-3′ (SEQ ID    NO:533)

In order to screen several libraries for a source of a full-lengthclone, DNA from the libraries was screened by PCR amplification with oneof the PCR primer pairs identified above. A positive library was thenused to isolate clones encoding the PRO361 gene using the probeoligonucleotide. RNA for construction of the cDNA libraries was isolatedfrom human fetal kidney tissue.

DNA sequencing of the clones isolated as described above gave thefull-length DNA sequence for PRO361 [herein designated as DNA45410-1250](SEQ ID NO:514) and the derived protein sequence for PRO361.

The entire nucleotide sequence of DNA45410-1250 is shown in FIG. 327(SEQ ID NO:514). Clone DNA45410-1250 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 226–228 and ending at the stop codon at nucleotide positions1519–1521 (FIG. 327). The predicted polypeptide precursor is 431 aminoacids long (FIG. 328). The full-length PRO361 protein shown in FIG. 328has an estimated molecular weight of about 46,810 daltons and a pI ofabout 6.45. In addition, regions of interest including the transmembranedomain (amino acids 380–409) and sequences typical of the arginasefamily of proteins (amino acids 3–14 and 39–57) are designated in FIG.328. Clone DNA45410-1250 has been deposited with ATCC and is assignedATCC deposit no. ATCC 209621.

Analysis of the amino acid sequence of the full-length PRO361polypeptide suggests that portions of it possess significant homology tothe mucin and/or chitinase proteins, thereby indicating that PRO361 maybe a novel mucin and/or chitinase protein.

Example 178 Isolation of cDNA Clones Encoding a Human PRO183, PRO184,PRO185, PRO5723, PRO3301 or PRO9940

DNA molecules encoding the PRO183, PRO184, PRO185, PRO5723, PRO3301 orPRO9940 polypeptides shown in the accompanying figures were obtainedthrough GenBank.

Deposit of Material

The following materials have been deposited with the American TypeCulture Collection, 10801 University Blvd., Manassas, Va. 20110-2209,USA (ATCC):

TABLE 10 Material ATCC Dep. No. Deposit Date DNA45410-1250 209621 Feb.5, 1998 DNA108722-2743 552-PTA Aug. 17, 1999 DNA142238-2768 819-PTA Oct.5, 1999 DNA40981-1234 209439 Nov. 7, 1997 DNA45419-1252 209616 Feb. 5,1998 DNA44196-1353 209847 May 6, 1998 DNA16422-1209 209929 Jun. 2, 1998DNA16435-1208 209930 Jun. 2, 1998 DNA21624-1391 209917 Jun. 2, 1998DNA23334-1392 209918 Jun. 2, 1998 DNA26288-1239 209792 Apr. 21, 1998DNA26843-1389 203099 Aug. 4, 1998 DNA26844-1394 209926 Jun. 2, 1998DNA30862-1396 209920 Jun. 2, 1998 DNA35680-1212 209790 Apr. 21, 1998DNA40621-1440 209922 Jun. 2, 1998 DNA44161-1434 209907 May 27, 1998DNA44694-1500 203114 Aug. 11, 1998 DNA45495-1550 203156 Aug. 25, 1998DNA47361-1154 209431 Nov. 7, 1997 DNA47394-1572 203109 Aug. 11, 1998DNA48320-1433 209904 May 27, 1998 DNA48334-1435 209924 Jun. 2, 1998DNA48606-1479 203040 Jul. 1, 1998 DNA49141-1431 203003 Jun. 23, 1998DNA49142-1430 203002 Jun. 23, 1998 DNA49143-1429 203013 Jun. 23, 1998DNA49647-1398 209919 Jun. 2, 1998 DNA49819-1439 209931 Jun. 2, 1998DNA49820-1427 209932 Jun. 2, 1998 DNA49821-1562 209981 Jun. 16, 1998DNA52192-1369 203042 Jul. 1, 1998 DNA52598-1518 203107 Aug. 11, 1998DNA53913-1490 203162 Aug. 25, 1998 DNA53978-1443 209983 Jun. 16, 1998DNA53996-1442 209921 Jun. 2, 1998 DNA56041-1416 203012 Jun. 23, 1998DNA56047-1456 209948 Jun. 9, 1998 DNA56050-1455 203011 Jun. 23, 1998DNA56110-1437 203113 Aug. 11, 1998 DNA56113-1378 203049 Jul. 1, 1998DNA56410-1414 209923 Jun. 2, 1998 DNA56436-1448 209902 May 27, 1998DNA56855-1447 203004 Jun. 23, 1998 DNA56859-1445 203019 Jun. 23, 1998DNA56860-1510 209952 Jun. 9, 1998 DNA56865-1491 203022 Jun. 23, 1998DNA56866-1342 203023 Jun. 23, 1998 DNA56868-1209 203024 Jun. 23, 1998DNA56869-1545 203161 Aug. 25, 1998 DNA56870-1492 209925 Jun. 2, 1998DNA57033-1403 209905 May 27, 1998 DNA57037-1444 209903 May 27, 1998DNA57129-1413 209977 Jun. 16, 1998 DNA57690-1374 209950 Jun. 9, 1998DNA57693-1424 203008 Jun. 23, 1998 DNA57694-1341 203017 Jun. 23, 1998DNA57695-1340 203006 Jun. 23, 1998 DNA57699-1412 203020 Jun. 23, 1998DNA57702-1476 209951 Jun. 9, 1998 DNA57704-1452 209953 Jun. 9, 1998DNA57708-1411 203021 Jun. 23, 1998 DNA57710-1451 203048 Jul. 1, 1998DNA57711-1501 203047 Jul. 1, 1998 DNA57827-1493 203045 Jul. 1, 1998DNA57834-1339 209954 Jun. 9, 1998 DNA57836-1338 203025 Jun. 23, 1998DNA57838-1337 203014 Jun. 23, 1998 DNA57844-1410 203010 Jun. 23, 1998DNA58721-1475 203110 Aug. 11, 1998 DNA58723-1588 203133 Aug. 18, 1998DNA58737-1473 203136 Aug. 18, 1998 DNA58743-1609 203154 Aug. 25, 1998DNA58846-1409 209957 Jun. 9, 1998 DNA58848-1472 209955 Jun. 9, 1998DNA58849-1494 209958 Jun. 9, 1998 DNA58850-1495 209956 Jun. 9, 1998DNA58853-1423 203016 Jun. 23, 1998 DNA58855-1422 203018 Jun. 23, 1998DNA59205-1421 203009 Jun. 23, 1998 DNA59211-1450 209960 Jun. 9, 1998DNA59213-1487 209959 Jun. 9, 1998 DNA59214-1449 203046 Jul. 1, 1998DNA59215-1425 209961 Jun. 9, 1998 DNA59220-1514 209962 Jun. 9, 1998DNA59488-1603 203157 Aug. 25, 1998 DNA59493-1420 203050 Jul. 1, 1998DNA59497-1496 209941 Jun. 4, 1998 DNA59588-1571 203106 Aug. 11, 1998DNA59603-1419 209944 Jun. 9, 1998 DNA59605-1418 203005 Jun. 23, 1998DNA59606-1471 209945 Jun. 9, 1998 DNA59607-1497 209957 Jun. 9, 1998DNA59609-1470 209963 Jun. 9, 1998 DNA59610-1559 209990 Jun. 16, 1998DNA59612-1466 209947 Jun. 9, 1998 DNA59613-1417 203007 Jun. 23, 1998DNA59616-1465 209991 Jun. 16, 1998 DNA59619-1464 203041 Jul. 1, 1998DNA59620-1463 209989 Jun. 16, 1998 DNA59625-1498 209992 Jun. 17, 1998DNA59767-1489 203108 Aug. 11, 1998 DNA59776-1600 203128 Aug. 18, 1998DNA59777-1480 203111 Aug. 11, 1998 DNA59820-1549 203129 Aug. 18, 1998DNA59827-1426 203089 Aug. 4, 1998 DNA59828-1608 203158 Aug. 25, 1998DNA59838-1462 209976 Jun. 16, 1998 DNA59839-1461 209988 Jun. 16, 1998DNA59841-1460 203044 Jul. 1, 1998 DNA59842-1502 209982 Jun. 16, 1998DNA59846-1503 209978 Jun. 16, 1998 DNA59847-1511 203098 Aug. 4, 1998DNA59848-1512 203088 Aug. 4, 1998 DNA59849-1504 209986 Jun. 16, 1998DNA59853-1505 209985 Jun. 16, 1998 DNA59854-1459 209974 Jun. 16, 1998DNA60283-1484 203043 Jul. 1, 1998 DNA60615-1483 209980 Jun. 16, 1998DNA60619-1482 209993 Jun. 16, 1998 DNA60621-1516 203091 Aug. 4, 1998DNA60622-1525 203090 Aug. 4, 1998 DNA60625-1507 209975 Jun. 16, 1998DNA60627-1508 203092 Aug. 4, 1998 DNA60629-1481 209979 Jun. 16, 1998DNA61755-1554 203112 Aug. 11, 1998 DNA61873-1574 203132 Aug. 18, 1998DNA62814-1521 203093 Aug. 4, 1998 DNA62872-1509 203100 Aug. 4, 1998DNA62876-1517 203095 Aug. 4, 1998 DNA62881-1515 203096 Aug. 4, 1998DNA64852-1589 203127 Aug. 18, 1998 DNA64884-1527 203155 Aug. 25, 1998DNA64890-1612 203131 Aug. 18, 1998 DNA65412-1523 203094 Aug. 4, 1998DNA66308-1537 203159 Aug. 25, 1998 DNA66309-1538 203235 Sep. 15, 1998DNA67004-1614 203115 Aug. 11, 1998 DNA68869-1610 203164 Aug. 25, 1998DNA68872-1620 203160 Aug. 25, 1998 DNA71159-1617 203135 Aug. 18, 1998

These deposits were made under the provisions of the Budapest Treaty onthe International Recognition of the Deposit of Microorganisms for thePurpose of Patent Procedure and the Regulations there under (BudapestTreaty). This assures maintenance of a viable culture of the deposit for30 years from the date of deposit and for at least five (5) years afterthe most recent request for the furnishing of a sample of the depositreceived by the depository. The deposits will be made available by ATCCunder the terms of the Budapest Treaty, and subject to an agreementbetween Genentech, Inc. and ATCC, which assures that all restrictionsimposed by the depositor on the availability to the public of thedeposited material will be irrevocably removed upon the granting of thepertinent U.S. patent, assures permanent and unrestricted availabilityof the progeny of the culture of the deposit to the public upon issuanceof the pertinent U.S. patent or upon laying open to the public of anyU.S. or foreign patent application, whichever comes first, and assuresavailability of the progeny to one determined by the U.S. Commissionerof Patents and Trademarks to be entitled thereto according to 35 USC §122 and the Commissioner's rules pursuant thereto (including 37 CFR §1.14 with particular reference to 886 OG 638).

The assignee of the present application has agreed that if a culture ofthe materials on deposit should die or be lost or destroyed whencultivated under suitable conditions, the materials will be promptlyreplaced on notification with another of the same. Availability of thedeposited material is not to be construed as a license to practice theinvention in contravention of the rights granted under the authority ofany government in accordance with its patent laws.

The foregoing written specification is considered to be sufficient toenable one skilled in the art to practice the invention. The presentinvention is not to be limited in scope by the construct deposited,since the deposited embodiment is intended as a single illustration ofcertain aspects of the invention and any constructs that arefunctionally equivalent are within the scope of this invention. Thedeposit of material herein does not constitute an admission that thewritten description herein contained is inadequate to enable thepractice of any aspect of the invention, including the best modethereof, nor is it to be construed as limiting the scope of the claimsto the specific illustrations that it represents. Indeed, variousmodifications of the invention in addition to those shown and describedherein will become apparent to those skilled in the art from theforegoing description and fall within the scope of the appended claims.

1. An isolated nucleic acid comprising: (a) a nucleic acid sequenceencoding the polypeptide of SEQ ID NO: 387; (b) a nucleic acid sequenceencoding the polypeptide of SEQ ID NO: 387, lacking its associatedsignal peptide; (c) the nucleic acid sequence of SEQ ID NO: 386; (d) thefull-length coding sequence of the nucleic acid sequence of SEQ ID NO:386; or (e) the full-length coding sequence of the cDNA deposited underATCC accession number
 203132. 2. The isolated nucleic acid of claim 1comprising a nucleic acid sequence encoding the polypeptide of SEQ IDNO:
 387. 3. The isolated nucleic acid of claim 1 comprising a nucleicacid sequence encoding the polypeptide of SEQ ID NO: 387, lacking itsassociated signal peptide.
 4. The isolated nucleic acid of claim 1comprising the nucleic acid sequence of SEQ ID NO:
 386. 5. The isolatednucleic acid of claim 1 comprising the full-length coding sequence ofthe nucleic acid sequence of SEQ ID NO:
 386. 6. The isolated nucleicacid of claim 1 comprising the full-length coding sequence of the cDNAdeposited under ATCC accession number
 203132. 7. An isolated nucleicacid encoding a polypeptide having at least 99% sequence identity to:(a) the amino acid sequence of the polypeptide of SEQ iD NO: 387; (b)the amino acid sequence of the polypeptide of SEQ ID NO: 387, lackingits associated signal peptide; (c) the amino acid sequence of thepolypeptide encoded by the full-length coding sequence of the nucleicacid sequence of SEQ ID NO: 386; or (d) the amino acid sequence of thepolypeptide encoded by the full-length coding sequence of the cDNAdeposited under ATCC accession number 203132; wherein said encodedpolypeptide induces chondrocyte redifferentiation.
 8. A vectorcomprising the nucleic acid of claim 7 or
 1. 9. The vector of claim 8,wherein said nucleic acid is operably linked to control sequencesrecognized by a host cell transformed with the vector.
 10. An isolatedhost cell comprising the vector of claim
 8. 11. The host cell of claim10, wherein said cell is a CHO cell, an E. coli or a yeast cell.